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Adding Carboplatin Increases PCR

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Topic: Adding Carboplatin Increases PCR
Posted By: 123Donna
Subject: Adding Carboplatin Increases PCR
Date Posted: Dec 13 2013 at 6:56pm

Additional drug shows promise for women with triple-negative breast cancer

http://www.eurekalert.org/multimedia/pub/65818.php?from=255866" rel="nofollow">

http://www.eurekalert.org/multimedia/pub/65818.php?from=255866" rel="nofollow"> IMAGE:  A new study suggests additional drug shows promise for women with triple-negative breast cancer.

http://www.eurekalert.org/multimedia/pub/65818.php?from=255866" rel="nofollow - Click here for more information.

SAN ANTONIO— In a nationwide study of women with "triple-negative" breast cancer, adding the chemotherapy drug carboplatin or the angiogenesis inhibitor Avastin to standard chemotherapy drugs brought a sharp increase in the number of patients whose tumors shrank away completely, investigators will report at the 2013 San Antonio Breast Cancer Symposium.

The results are especially promising in the case of carboplatin, study leaders say, as Avastin has shown little effectiveness as a long-term preventer of cancer recurrence. The study is scheduled to be presented Friday, December 13, at 9:30 a.m., CT.

"Our findings suggest that carboplatin could be used either in addition to or instead of some of the drugs in the standard chemotherapy regimen for women with triple-negative breast cancer," says the study's senior author, Eric Winer, MD, chief of the division of Women's Cancers in the Susan F. Smith Center for Women's Cancers at Dana-Farber Cancer Institute.

Triple-negative breast cancer, named for the lack of three growth-spurring receptors on its cells' surface, accounts for 15 to 25 percent of all breast cancer cases. Although it often goes into remission in response to chemotherapy, it can be more aggressive and more likely to recur than other breast cancers. Because of the dearth of three common receptors on the cell surface, triple-negative cancers usually aren't vulnerable to drugs that block these receptors in other types of breast cancer.

The current study involved 450 women with stage II or III triple-negative breast cancer. It was sponsored by the Cancer and Leukemia Group B, which is part of the Alliance for Clinical Trials in Oncology, a national clinical research network supported by the National Cancer Institute. As a pre-surgery treatment, the women were randomly assigned to receive either standard chemotherapy (a combination of paclitaxel, adriamycin, and cyclophosphamide), standard chemotherapy plus carboplatin, standard chemotherapy plus Avastin (a drug that blocks cancers from generating blood vessels), or standard chemotherapy plus both carboplatin and Avastin.

Among patients who received standard chemotherapy alone, 34 percent had their tumors disappear. That compares with 48 percent of patients in the chemotherapy plus carboplatin group, 51 percent those in the chemotherapy plus Avastin group, and 61 percent of those in the chemotherapy plus carboplatin and Avastin group.

Promising as the results are, "more research is needed to determine which women with triple-negative breast cancer particularly benefit from added carboplatin and which do not," says Winer. "As we learn more about triple-negative breast cancer, we'll be better able to determine which set of drugs is most effective for individual patients.

###

The lead author of the study is William Sikov, MD, of Brown University. Co-authors are Donald Berry, PhD, of University of Texas M.D. Anderson Cancer Center; Charles Perou, PhD, and Lisa Carey, MD, of UNC Lineberger Comprehensive Cancer Center, Chapel Hill, N.C.; Baljit Singh, MBBS, MD, of New York University Medical Center; Constance Cirrincione, MD, Alliance Statistical Center, Durham, N.C.; Sara Tolaney, MD, MPH, Mehra Golshan, MD, and Jennifer Bellon, MD, of Dana-Farber; Charles Kuzma, MD, of Southeast Cancer Control Consortium, Winston-Salem, N.C.; Tim Pluard, MD, of Washington University-St. Louis Medical Center; George Somlo, MD, of City of Hope Comprehensive Cancer Center; Elisa Port, MD, of Mount Sinai Medical Center, New York, N.Y.; Deborah Collyar of Patient Advocates in Research, Danville, Calif.; Olwen Hahn, MD, of University of Chicago Medical Center; and Clifford Hudis, MD, of Memorial Sloan-Kettering Cancer Center.

http://www.eurekalert.org/pub_releases/2013-12/dci-ads120613.php#.UqtrghRjhhk.scoopit" rel="nofollow - http://www.eurekalert.org/pub_releases/2013-12/dci-ads120613.php#.UqtrghRjhhk.scoopit



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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15




Replies:
Posted By: 123Donna
Date Posted: Dec 13 2013 at 8:46pm

Carboplatin Yes, Bevacizumab No for Triple-Negative Breast Cancer

SAN ANTONIO — Adding carboplatin to paclitaxel in the neoadjuvant setting for triple-negative breast cancer significantly improves pathologic complete response (pCR) rates. So, for that matter, does adding bevacizumab (Avastin) — somewhat.

The catch is that bevacizumab adds only an incremental benefit, does not have synergistic activity with carboplatin, and is associated with significantly increased toxicities that could outweigh the benefit, said William M. Sikov, MD, from the Warren Alpert Medical School of Brown University in Providence, Rhode Island.

"Should carboplatin be routinely added to stage II or III triple-negative breast cancer? With the caveat...that we do not have long-term results — I think if you're looking in the neoadjuvant setting, my answer to that question would be yes," Dr. Sikov said in a media briefing prior to his presentation.

He explained that carboplatin improved the pCR rate, but it is not known if that will result in significant improvement in recurrence-free or overall survival.

Although bevacizumab also increased the pCR rate, it came "at the cost of significant toxicities, and I don't think it should be routinely added to neoadjuvant chemotherapy," he said.

Jeffrey B. Smerage, MD, PhD, a breast cancer specialist from the University of Michigan Comprehensive Cancer Center in Ann Arbor, who was not involved in the study, told Medscape Medical News that "Dr. Sikov's comments make a lot of sense to me."

He noted that the addition of carboplatin to a standard neoadjuvant regimen "clearly" showed evidence of an increase in pCR.

Even without long-term data, the results are helpful to clinicians, he suggested.

Dr. Smerage explained that in the neoadjuvant setting, patients tend to have larger tumors, often have clinically positive lymph nodes, and generally have higher risks at baseline.

"It's also a setting in which your goal is response. Maybe the goal is to allow a more effective surgery, even if the surgery is going to be a mastectomy.... Maybe your goal is to be able to attempt a lumpectomy, where the goal of that therapy is response but not necessarily prolonged progression-free survival," he said.

Tough Nut to Crack

Triple-negative breast cancers — so called because they lack the drug targets of estrogen, progesterone, and HER2 receptors — comprise approximately 20% of breast cancers, and are more common in blacks, Hispanics, younger women, and those with BRCA1 mutations.

Although there have been advances in chemotherapy in the adjuvant setting, patients with triple-negative disease still have worse prognoses than patients with either estrogen-receptor-positive orHER2-positive tumors. Median overall survival for patients with advanced triple-negative cancers is less than 1 year, Dr. Sikov said.

In the neoadjuvant setting, evidence of a benefit in women with triple-negative disease comes from a meta-analysis presented at last year's SABCS ( http://cancerres.aacrjournals.org/cgi/content/meeting_abstract/72/24_MeetingAbstracts/S1-11" rel="nofollow - abstract S1-11 ). That study showed that 34% of patients had a pCR with neoadjuvant chemotherapy and a better clinical course than women with similar tumors who had residual disease going to surgery.

Dr. Sikov's team chose to study carboplatin for 2 reasons: its activity in patients with BRCA mutation-related cancers, which are similar to sporadic triple-negative cancers in several respects; and the high pCR rates in pilot studies in which carboplatin was added to standard chemotherapy in patients with triple-negative tumors.

2 × 2 Design

The CALGB 40603 study was a randomized phase 2 trial with a 2 × 2 randomization scheme in which all patients received paclitaxel 80 mg/m˛ weekly for 12 weeks, plus 1 of 3 treatments: bevacizumab 10 mg/kg every 2 weeks for 9 cycles; carboplatin to the area under the curve (AUC) 6 every 3 weeks for 4 cycles; or both carboplatin and bevacizumab.

All patients went on to dose-dense chemotherapy with doxorubicin and cyclophosphamide for 4 cycles.

The trial was designed to look at pCR rates in the breast and axilla, but was not powered to compare individual treatment groups or to detect differences in recurrence-free or overall survival, Dr. Sikov noted.

A total of 443 patients were enrolled, and 427 went on to surgery and were included in the pCR analysis. (Dr. Sikov explained that progression-free and overall survival will be reported at a later date.)

Rates of pCR in the breast were lower in patients who did not receive carboplatin than in those who did (46% vs 60%). The odds ratio (OR) for carboplatin was 1.76 (P = .001).

Rates of pCR in the breast were also lower in patients who did not receive bevacizumab than in those who did (48% vs 59%). The OR for the angiogenesis inhibitor was 1.58 (P = .0089).

However, there was no evidence of a synergistic interaction between the carboplatin and bevacizumab, the investigators found.

Looking at pCR in the breast and axillary lymph nodes, they again saw an effect on pCR in women treated with carboplatin, compared with those who were not (41% vs 54%). The OR for carboplatin in the breast/axilla was 1.71 (= .0029). The same pattern was seen with bevacizumab (44% vs 52%). The OR was 1.36, but it just missed being statistically significant (= .057)

Again, the investigators saw no evidence of synergy in the effect of the drugs on pCR in the breast and axilla combined.

Bevacizumab in this study was also associated with increases in grade 3 toxicities, including hypertension, febrile neutropenia (especially with carboplatin), serious infections despite a normal absolute neutrophil count, bleeding, and thromboembolic and surgical complications.

"We await results of correlative studies, including subtype analysis, to see if we can identify markers of response or resistance to standard neoadjuvant chemotherapy, as well as to the addition of carboplatin or bevacizumab," Dr. Sikov said.

The study was funded by the National Cancer Institute, Genentech, and the Breast Cancer Research Foundation. Dr. Sikov and Dr. Smerage have disclosed no relevant financial relationships.

36th Annual San Antonio Breast Cancer Symposium (SABCS): Abstract S5-01. Presented December 13, 2013.

http://www.medscape.com/viewarticle/817820" rel="nofollow - http://www.medscape.com/viewarticle/817820



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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Jan 11 2014 at 11:31am
Slide Show: 2013 San Antonio Breast Cancer Symposium - See more at: http://www.cancernetwork.com/conference-report/slide-show-2013-san-antonio-breast-cancer-symposium#sthash.qRaAEgHf.4cuysgmV.dpuf

Adding Carboplatin to a Neoadjuvant Chemotherapy Regimen in Triple-Negative Breast Cancer Patients Boosts Pathologic Complete Response Rates

A randomized phase II trial of 454 patients shows that  http://www.cancernetwork.com/sabcs-2013/neoadjuvant-combo-effective-triple-negative-breast-cancer" rel="nofollow - adding both bevacizumab and carboplatin  to a standard neoadjuvant chemotherapy backbone increases pathologic complete response (pCR) in patients with triple-negative breast cancer. In the neoadjuvant setting, pCR is associated with improved recurrence-free survival and overall survival. However, bevacizumab also increased high-grade adverse events, including post-surgery complications. The boost in pCR rates when bevacizumab was combined with carboplatin was additive but not synergistic. Patients in the study continue to be followed for long-term recurrence and survival rates.

Source: Sikov WM, Berry DA, Perou CM, et al. Impact of the addition of carboplatin (Cb) and/or bevacizumab (B) to neoadjuvant weekly paclitaxel (P) followed by dose-dense AC on pathologic complete response (pCR) rates in triple-negative breast cancer (TNBC): CALGB 40603 (Alliance). SABCS 2013; Abstract S5-01.

- See more at: http://www.cancernetwork.com/conference-report/slide-show-2013-san-antonio-breast-cancer-symposium#sthash.qRaAEgHf.4cuysgmV.dpuf



http://www.cancernetwork.com/sabcs-2013/neoadjuvant-combo-effective-triple-negative-breast-cancer" rel="nofollow - http://www.cancernetwork.com/sabcs-2013/neoadjuvant-combo-effective-triple-negative-breast-cancer


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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Apr 08 2014 at 10:28pm
SABCS 2013 
Better Neoadjuvant Regimens With Carboplatin
Trials show benefit for triple-negative breast cancer
http://www.clinicaloncology.com/ViewArticle.aspx?d=Solid%2BTumors&d_id=148&i=April+2014&i_id=1052&a_id=26279" rel="nofollow - http://www.clinicaloncology.com/ViewArticle.aspx?d=Solid%2BTumors&d_id=148&i=April+2014&i_id=1052&a_id=26279



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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: lizziealberta
Date Posted: Apr 23 2014 at 2:03am
Has anyone on this forum had this therapy. I am in process of deciding on chemo so could use the input. Thank much!

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ER+ misdiagnosed 09, was ER+/TNBC,lumpectomy, C/T, rads, AI. TNBC in node 4/14, in neoadjuvant A/C then carbo/gemzar, complete path response. double mastectomy.


Posted By: atlhoosier
Date Posted: Apr 23 2014 at 2:01pm
I am currently undergoing taxol & carboplatin.  I've had 8 doses of taxol and 3 of carboplatin.  I have 1 more treatment of carbo and 4 of the taxol.  Then I will have 4 treatments of A/C.  

Next Friday I will have a mammogram to see the progress.  I'll be sure to let you know!

PS...I'm sorry your dog died the same day!  :(


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DX Jan 2014, 37yo
TNBC, Stage 2A, 4 tumors, BMX Aug 2014, clear margins

2017 - Mets to lung (single nodule) & sacrum
1st line(current): clinical study w/ taxol & reparixin (may be placebo)


Posted By: 123Donna
Date Posted: May 14 2014 at 9:10pm
New way to predict response to chemo in triple-negative breast cancer
Researchers from University Hospitals (UH) Case Medical Center's Seidman Cancer Center will present findings from a study that found the presence of tumor-infiltrating lymphocytes, a type of white blood cell, ahead of treatment may help predict response to platinum-based chemotherapy in women with triple-negative breast cancer. The data are being presented at the 50th American Society for Clinical Oncology (ASCO) Annual Meeting in Chicago.

"Triple-negative breast cancers tend to be more aggressive compared to other types of breast cancers, and being able to predict response to therapy could greatly impact treatment decisions and patient outcomes," says study author Shaveta Vinayak, MD, oncologist at UH Case Medical Center and Assistant Professor at Case Western Reserve University School of Medicine. "Our research shows that the presence of  http://medicalxpress.com/tags/lymphocytes/" rel="nofollow - lymphocytes before administering chemotherapy could predict a positive response to platinum-based therapy."

Triple negative breast cancers are those that do not have estrogen or progesterone receptors, and do not have an excess of the HER2 protein on the cancer cell surfaces. This makes it more difficult to treat because the hormone-blocking or the HER2-targeting treatments do not work. Triple negative breast cancers tend to occur more often in younger women and in African-American women.

Platinum-based therapies are being tested in clinical trials for  http://medicalxpress.com/tags/triple-negative+breast+cancer/" rel="nofollow - triple-negative breast cancer , and evaluation of tumor-infiltrating lymphocytes is an important factor in determining response to this treatment. For oncologists, this could provide a new tool to individualize treatment for these women.

Researchers from various institutions in the Eastern Cooperative Oncology Group, one of the largest clinical cancer research organizations in the United States that conducts clinical trials in all types of adult cancers, contributed to this analysis. Funding for this study was provided by Breast Cancer Research Foundation, ASCO Conquer Cancer Foundation, Triple-Negative Breast Cancer Foundation, Myriad Genetics, and National Institutes of Health (Stanford CTSA).

About the Study

Oral Abstract Session

Breast Cancer - Triple-Negative/Cytotoxics/Local Therapy

Abstract #1024: June 3, 9:45 AM - 12:45 PM

Dr. Vinayak will present new findings from the PrECOG 0105 trial, a trial evaluating neoadjuvant platinum-based chemotherapies – carboplatin, gemcitabine and iniparib – in women with triple-negative breast cancer. This correlative study assessed the association of tumor-infiltrating lymphocytes in pre-treatment breast cancer tissue with pathologic response to treatment.

The trial evaluated 70 patients with triple-negative breast cancer who had completed at least 4 of 6 planned cycles of therapy. Tissue and tumor sections from pre-chemotherapy biopsies were evaluated by a central pathologist for density of lymphocytes. Pathologic response was assessed by the residual cancer burden index.

Results showed that tumor-infiltrating lymphocytes found in the connective tissue and the tumor itself are predictive of response to platinum-based neoadjuvant chemotherapy and are significantly associated with triple-negative  http://medicalxpress.com/tags/breast+cancer/" rel="nofollow - breast cancer subtypes, with the highest frequency in the immunomodulatory subtype.

http://medicalxpress.com/news/2014-05-response-chemo-triple-negative-breast-cancer.html" rel="nofollow - http://medicalxpress.com/news/2014-05-response-chemo-triple-negative-breast-cancer.html




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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: mimsey
Date Posted: May 15 2014 at 5:47pm
Mastectomy  Feb
I am having Carboplatin right now ..with Taxol....
Followed by  A/C
Than radiation 


Posted By: MomMom44
Date Posted: May 16 2014 at 3:51pm
Mimsey,
 
Welcome to the thread.  What is your diagnosis?  My MO initially suggested that she might add Carboplatin to the Taxol, but decided later it wasn't necessary.  As you can see from my signature, I've completed 4 DD AC and yesterday had my third of 12 weekly Taxol.
 
Are you finding the Carbo & Taxol to be tolerable?
 
 


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DX TNBC 1/14; age 66; Stage 1; Grade 2; 1.2 cm; 0/2 nodes; lumpectomy; BRAC Neg; 4 DD AC; Completed 12 weekly Taxol July 2014; Radiation August 2014


Posted By: 123Donna
Date Posted: Jun 30 2014 at 5:03pm
Bumping for new members


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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: rosewater
Date Posted: Jul 01 2014 at 2:08am
Many thanks to you, Donna, for bringing this thread to my attention.

Mimsey, I too am curious to hear more about how treatment with Taxol and Carboplatin has been for you. I'm also interested in how you came to the decision to add Carboplatin. My oncologist is considering adding it for me as well (in 3 weeks), but in the adjuvant setting, rather than in the neoadjuvant setting (as with the clinical trials).

I'm curious if anyone else has tried this drug yet, and if anyone has tried it in the adjuvant setting??

Thank you!
rosewater


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DX IDC TNBC 03/14 age 40, Stage 1, Grade 3, 2cm, 0/4Nodes, lumpectomy 04/14, DD A/C x4, Taxol x12, Carboplatin x2, BMX 10/14, rads x28 Finished Jan 14/15, Oopherectomy Jan 29/15 BRCA 2+


Posted By: 123Donna
Date Posted: Jul 01 2014 at 8:25am
Rosewater,

This may or may not help with the information you are asking.  I did not have Carbo for my initial treatment in 2009.  When I had my recurrence in 2010, I entered a clinical trial that included Carboplatin and Gemzar with a trial drug.  The internal mammary node was not removed surgically so we hoped the drugs would do their job in an adjuvant setting.  After 2 rounds, the scan showed no evidence of disease.  I went on to have 2 more rounds then 40 rounds of radiation.  

Donna


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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: littleradish
Date Posted: Jul 01 2014 at 3:21pm
Rosewater

I had TC neo-adjuvant and after my mastectomy they still found 50% of the tumor. We thought it was gone but apparently it became like swiss cheese and could not be seen on ultrasound so they suggested more chemo.
I was given cisplatin and gemzar in the adjuvant setting.



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Diagnosed March 2013, TC chemo from April-July 4 rounds. Double mastectomy Aug of 2013 clear margins and no lymph nodes involved. 4 rounds of gemzar and cisplatin September to October


Posted By: rosewater
Date Posted: Jul 01 2014 at 3:28pm
Thank you, Donna and littleradish!

It's sooo interesting how everyone reacts to these drugs!!




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DX IDC TNBC 03/14 age 40, Stage 1, Grade 3, 2cm, 0/4Nodes, lumpectomy 04/14, DD A/C x4, Taxol x12, Carboplatin x2, BMX 10/14, rads x28 Finished Jan 14/15, Oopherectomy Jan 29/15 BRCA 2+


Posted By: Lillie
Date Posted: Jul 01 2014 at 7:40pm
Hi Rosewater,
I did an adjuvant clinical trial of Dose Dense Cytoxan and Adriamician(sp)x 4 followed by Dose Dense Taxol and Gemzar x 4. Since I had a mastectomy first, no radiation was done. I did have micromets in 1 lymph node which was removed when I had the mastectomy.

I think there is something about getting the cisplatin, carboplatin or gemzar that can be a good thing.

Just my opinion.

God Bless,
Lillie

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Dx 6/06 age 65,IDC-TNBC
Stage IIb,Gr3,2cm,BRCA-
6/06 L/Mast/w/SNB,1of3 Nodes+
6/06 Axl. 9 nodes-
8/8 thru 11/15 Chemo (Clin-Trial) DD A/Cx4 -- DD taxol+gemzar x4
No Rads.
No RECON - 11/2018-12 yrs NED


Posted By: JackiWalkr
Date Posted: Jul 02 2014 at 12:50pm
I am currently taking Carboplatin and Taxol. I had 1 treatment of the combo and we can't feel lump anymore. Since then I have had 2 more combo's and 1 Taxol. I have been postponed 1 week due to low liver levels from Taxol and 4 weeks due to low neutrophils from Carboplatin. Even had blood transfusion with 2 bags. I am back on schedule with modified doses and extra week of recovery. I have 1 Carboplatin/Taxol combo left and 7 Taxol doses. Modified dose of 600 mg Carbo and 100mg Taxol was a breeze compared to first dose of 714 mg Carbo and 134 mg Taxol.

Jackie

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DX IDC TNBC 3/31/14 Age 46 Stage 2a, Grade 3, 2.1cm, 0 nodes, (4)Carbo(5)Taxol. AC DD 4 of 4. Lumpectomy 10/30/2014 NED. 33 Rads 2/12/15. BRCA 1/2 normal=negative


Posted By: sweetjam
Date Posted: Jul 06 2014 at 5:17pm
I had 6 treatments of carboplatin and taxol every 3 weeks. My tumor initially grew after 2 rounds or sometime before I started chemo. They told me the tumor still had 10% cancer in it when they took it out. Just hoping the chemo has done its job. There has been no talk of rads because I had both breast removed.

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DX 1/17/14 TN IDC, Stage 1 Grade 2, 1.4cm, Age 50, BRCA -, Started Chemo 2/10 C/T, every 3 weeks. Last Chemo 5/23/14. Double Mastectomy 6/23 3/4 nodes all negative. 6/23 final path tumor ER+, PR+,


Posted By: JMJ
Date Posted: Jul 08 2014 at 5:16pm
I had 4 doses AC followed by 12 weeks of taxol and carboplatin every 3 weeks. I have one more carbo to go and 5 more taxols. I skipped one week of taxol due to low WBC count the week after my second taxol/carbo they added the taxol I missed onto the end of treatment. I had my mastectomy first but had I gone to the facility I am receiving treatment at first, they would have had me do chemo first. I transferred care after my unilateral mastectomy. I started chemo within 30 days of surgery though and my dr added lupron shots every 4 weeks. I had 3 positive lymph nodes. The 3rd node was considered micromets. I will have rads because my tumor was 4.6 cm and my smallest margin was less than a mm. I also had lymph vascular invasion and necrosis.

I have tolerated everything well, I had some nausea with the AC and am more tired with the taxol/carbo. I had one week my platelets were boarder line, that was the week before my WBC count was too low. I have had some neuropathy in my feet with the carbo/taxol. I am taking L-glutamine and B6 to help with that, other supplements they are having me take are calcium and vit D. My initial vit D was 18. I should mention for me the hardest part has been the chemo brain.

I hope everyone is doing well!
+JMJ+


Posted By: tmariee
Date Posted: Jul 22 2014 at 6:10pm
Hi everybody!  I just joined the forum, having completed 4 rounds of AC and 10 rounds of Taxol plus Carboplatin for TNBC.  I was diagnosed in Dec of 2013, lumpectomy 1/6/14, followed by brachytherapy (SAVI) two weeks later.  I did 4 rounds of AC starting 2/21/14, and then added Carboplatin to the 12 weekly rounds of Taxol that was to follow.  We knew that adding the Carbo may increase the efficacy of treatment, but also may increase the stress on my bone marrow.  After round 10 my platelet count dropped such that I couldn't do another infusion,  and remained too low for 3 more weeks.  At that point (last week) my Oncologist decided that my bone marrow has had enough and told me that I'm done with chemo.  I asked about the consequences of doing 10 instead of 12 rounds, and he told me that the newest research indicates that the Carboplatin may be just as or more important than the Taxol, and that I had done a LOT of chemo.  My last infusion was 4 weeks ago.  I'm starting to regain my energy (in baby steps), and I'm also starting to see some hair sprout on my noggin. 

My tumor was stage 2 (just over 2 cm), grade 3, with clean margins and with 0/4 lymph nodes affected.  They found it on my yearly mammo; I had no symptoms and didn't feel anything until I knew it was there.  

I've recently read about a promising clinical trial at MD Anderson for a vaccine to prevent recurrence.  Anybody know anything about this?  I've put in a message to my Onco doc inquiring about it this morning.


Posted By: Linda428
Date Posted: Jul 22 2014 at 6:54pm
X


Posted By: rosewater
Date Posted: Jul 22 2014 at 7:15pm
Hi tmariee,

Your post is very timely for me, as I just got home from meeting with my oncologist. Previously, my onc told me that depending on how I was doing on the taxol (weekly for 12 weeks), she could start adding carboplatin to my regimen (every 3 weeks). She was just at a conference, and she said she was talking with the oncologists there, and most of them are saying that the science just isn't there for carboplatin in the adjuvant setting. I don't think she's as keen to put me on it now, but the other thing is that she is concerned that it might bring my white blood cell count, or my platelets(?) (I can't remember now!) down too far. The other thing, is that, being in Canada, she has to apply for the Cancer Agency to agree to give me the drug - this is rather annoying, as I didn't know that was the case. So, now it's in the hands of the agency, of whether or not, they believe they should provide it for me. My next chemo is tomorrow, so it I may or may not get it - or, I could possibly get it next week instead...

I'm curious, did you have carboplatin every week for 12 weeks along with your taxol? or just a few times?

I'm concerned about having to miss chemo if my cell count goes down too far, but I'm also concerned about not trying everything possible...

On a positive note, my onc told me that she has many TN patients that have survived and are doing very well - so that was good to hear.

Hugs,
rosewater

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DX IDC TNBC 03/14 age 40, Stage 1, Grade 3, 2cm, 0/4Nodes, lumpectomy 04/14, DD A/C x4, Taxol x12, Carboplatin x2, BMX 10/14, rads x28 Finished Jan 14/15, Oopherectomy Jan 29/15 BRCA 2+


Posted By: tmariee
Date Posted: Jul 23 2014 at 8:18am
Hi Rosewater,
Yes, I did taxol and carboplatin every week for a total of 10 weeks. 3 times I had to do Neulasta shots for 3 days post infusion to raise my WBC and Neutrophil counts, which I tolerated well. My Onco doc told me that raising my platelet count was not so easy, which is why he stopped when my platelets dropped and didn't recover on their own after 3 weeks. They did come back up in the last week, just not enough, and my neutrophils dropped in the last week even though I didn't have chemo. I'm thinking I'll get a CBC done next week to see where I'm at.

I am concerned about not having done the last 2 treatments, but it is what it is. I'm hoping that 10 weeks of taxol plus carboplatin are at least as effective as 12 weeks of taxol only. One foot in front of the other, I'm moving forward.

Tmariee


Posted By: 123Donna
Date Posted: Aug 09 2014 at 12:30pm
Bumping for new members

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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: rosewater
Date Posted: Aug 12 2014 at 7:26pm
Hi everyone,
So, I have my 7th taxol treatment tomorrow...there's been lots of discussion between my onc & myself of whether or not to add the carboplatin to my taxol regimen. The Cancer agency here has not approved the request to give it to me given that the science is not there to support carboplatin in the adjuvant setting. My onc told me yesterday that she could give it to me if I purchased it myself. I told her I would be willing to do that, but she then went on to say that she was not very keen to give it to me considering that my white blood cell count is just borderline now, and she thinks it would be too hard on my bone marrow. I have a call out to her now asking if neupogin shots would help...I'm just wanting to make sure I've covered all the angles before saying "no" to this drug. I don't want to kick myself later for not trying it, but I also don't want to kick myself now for trying it, then having to stop my taxol treatments. Basically, I just don't want to kick myself :)

I'm wondering if any of you have any input to ease my mind. My chemo is tommorrow. I also haven't been able to figure out if carboplatin HAS to be done with the taxol - is the efficacy supposedly better with the two together (though, I think that Donna had it with gemzar)? Could I do it later if my white bood cells come up higher?

My onc also mentioned that if my BRCA results come back positive, she could possily give me cisplatin while I'm getting my radiation...I have not heard much about cisplatin yet, and not sure if she would give the carboplatin with rad...

The other thing she mentioned, is that just yesterday, she receiced an email stating that there is a clinical trial starting in the new year for carboplatin in the adjuvant setting. Too late for me, but still intersting...

Thanks in advance for your input!!

Rosewater

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DX IDC TNBC 03/14 age 40, Stage 1, Grade 3, 2cm, 0/4Nodes, lumpectomy 04/14, DD A/C x4, Taxol x12, Carboplatin x2, BMX 10/14, rads x28 Finished Jan 14/15, Oopherectomy Jan 29/15 BRCA 2+


Posted By: rosewater
Date Posted: Sep 04 2014 at 10:53pm
So, I just finished my 10th weekly taxol injection - this time the Cancer Agency also agreed to add Carboplatin (adjuvant setting). Since I only have 2 more taxols to go, it looks like I'll only be having the one Carboplatin treatment. Seems kind of weird, but maybe better than not at all? I have no idea. Just hoping I don't get nausea from adding the carbo today. For those that added Carboplatin to their Taxol, did you take many anti-nausea drugs for the first couple days? I've had 1 Ondansetron, and will take another before I go to bed. The nurse also gave me a couple Dexamethasone's to take, but I'm wary to take them given the recent study that Donna posted that mentioned that Dexamethasone may reduce pacletaxel - induced tumor cell apoptosis, so I feel more willing to have some nausea than take additional Dexamethasone pills. Anyone else have issues wth nausea while taking Carboplatin? Thinking about trying gravol instead if the nausea arrises...any advice or tips greatly appreciated.

Many thanks,
Roewater

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DX IDC TNBC 03/14 age 40, Stage 1, Grade 3, 2cm, 0/4Nodes, lumpectomy 04/14, DD A/C x4, Taxol x12, Carboplatin x2, BMX 10/14, rads x28 Finished Jan 14/15, Oopherectomy Jan 29/15 BRCA 2+


Posted By: 123Donna
Date Posted: Dec 12 2014 at 10:40pm
http://www.medpagetoday.com/MeetingCoverage/SABCS/49094" rel="nofollow - http://www.medpagetoday.com/MeetingCoverage/SABCS/49094

http://www.medscape.com/viewarticle/836438" rel="nofollow - http://www.medscape.com/viewarticle/836438




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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Dec 12 2014 at 10:46pm
Combination of carboplatin and chemotherapy improves outcomes for triple-negative breast cancer patients

In a clinical trial involving women with triple-negative breast cancer, patients who received the drugs carboplatin and/or bevacizumab in combination with standard chemotherapy prior to surgery were more likely to have their tumors disappear entirely from the breast, according to data presented by investigators during the 2014 San Antonio Breast Cancer Symposium.

Although bevacizumab doesn't reduce long-term rates of cancer recurrence, the results raise hopes that carboplatin can be an important part of the fight against triple-negative cancer, say the leaders of the study, which was organized by the Alliance for Clinical Trials in Oncology with extensive involvement of physician/scientists at Dana-Farber Cancer Institute.

The investigators analyzed data from 360 patients with triple-negative breast cancer, the vast majority of whom had a form of the disease known as basal-like tumors. Triple-negative cancer, named for its cells' lack of three key receptors, accounts for about 15-20 percent of all breast cancers and tends to be aggressive, but can often be treated successfully if caught early. Basal-like tumors are made up of cells that resemble the basal cells lining the milk ducts.

In the trial, patients with triple-negative breast cancer were treated with "neoadjuvant" chemotherapy — which helps shrink tumors so they can be surgically removed — either alone or in combination with bevacizumab or carboplatin or both. (Bevacizumab prevents tumors from developing networks of blood vessels; carboplatin is a platinum-based chemotherapy agent.)

The researchers found that 61 percent of patients with basal-like tumors who received a combination of carboplatin and chemotherapy experienced a pathologic complete response — no microscopic evidence of cancer in the breast following surgery to remove tumor tissue — compared to 47 percent of those who received chemotherapy alone. Roughly the same improvement was seen in patients with other types of triple-negative breast cancer.

"In general, patients with triple-negative breast cancer who have a pathological complete response (pCR) with neoadjuvant chemotherapy are much less likely to experience a recurrence," says the study's senior author,  http://doctors.dana-farber.org/directory/profile.asp?dbase=main&setsize=50&last_name=winer&grouptype_typeid_data=1&gs=c&nxtfmt=c&display=Y&pict_id=0000262" rel="nofollow - Eric Winer, MD , director of  http://www.dana-farber.org/Adult-Care/Treatment-and-Support/Treatment-Centers-and-Clinical-Services/Breast-Cancer-Treatment-Center.aspx" rel="nofollow - Breast Oncology  at the  http://www.dana-farber.org/Adult-Care/Treatment-and-Support/Treatment-Centers-and-Clinical-Services/Susan-F--Smith-Center-for-Women-s-Cancers.aspx" rel="nofollow - Susan F. Smith Center for Women's Cancers at Dana-Farber . "While we are optimistic about the role of carboplatin in triple negative breast cancer, we still do not know if it will lead to a high cure rate. Ongoing studies are addressing this issue and attempting to determine how and in whom to use carboplatin."

Funding for the study was provided by the National Cancer Institute, Roche-Genentech, and the Breast Cancer Research Foundation.

http://www.healthcanal.com/cancers/breast-cancer/58341-combination-of-carboplatin-and-chemotherapy-improves-outcomes-for-triple-negative-breast-cancer-patients.html" rel="nofollow - http://www.healthcanal.com/cancers/breast-cancer/58341-combination-of-carboplatin-and-chemotherapy-improves-outcomes-for-triple-negative-breast-cancer-patients.html



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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Dec 15 2014 at 9:32pm
Research: Two drugs before surgery help women with triple-negative breast cancer

breast cancer specialist and clinical researcher at Women & Infants Hospital of Rhode Island presented research yesterday at the 2014 San Antonio Breast Cancer Symposium showing that adding either thechemotherapy drug carboplatin or the blood vessel-targeting drug bevacizumab to the standard treatment of chemotherapy before surgery helped women who have the basal-like subtype of triple-negative breast cancer.

"We found that adding either carboplatin or bevacizumab to standard preoperative chemotherapy increased pathologic complete response rates for women with basal-like cancers - that is, it increased the proportion of women who had no residual cancer detected at surgery. At the same time, we found that while carboplatin had a similar effect in the smaller group of triple-negative patients with nonbasal-like cancers, adding bevacizumab actually decreased response rates for women with nonbasal-like cancers," says William M. Sikov, MD, associate chief of clinical research with the Program in Women's Oncology at Women & Infants and associate professor of medicine at The Warren Alpert Medical School of Brown University.

Last year, Sikov and colleagues reported in a randomized, phase II clinical trial called CALGB/Alliance 40603 that adding either carboplatin or bevacizumab to standard preoperative chemotherapy increased pathologic complete response rates in 443 women with operable stage II or III triple-negative breast cancer. These latest results are based on analysis of tissue samples obtained before patients started treatment, correlated with findings at surgery after treatment. Pretreatment tumor samples from 360 of the patients showed that 314 were basal-like and 46 nonbasal-like.

"We have also looked at expression of variety of gene signatures in the pretreatment tissue samples to determine if they benefit from the addition of bevacizumab or carboplatin" Sikov says. "We found that gene signatures characteristic of high proliferation rates and low estrogen-receptor signaling, which are both considered characteristics of more aggressive disease, are associated with higher rates of response rates overall and increased benefit from adding bevacizumab."

http://www.sciencecodex.com/research_two_drugs_before_surgery_help_women_with_triplenegative_breast_cancer-147535" rel="nofollow - http://www.sciencecodex.com/research_two_drugs_before_surgery_help_women_with_triplenegative_breast_cancer-147535


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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: May 12 2015 at 6:39pm
bumping for new members



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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: May 12 2015 at 6:48pm
Optimizing Chemotherapy in Triple-Negative Breast Cancer: The Role of Platinum

http://meetinglibrary.asco.org/content/11400037-144" rel="nofollow - http://meetinglibrary.asco.org/content/11400037-144




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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: May 14 2015 at 8:40am
Platinum chemos may benefit TNBC patients who are also BRCA Negative.

Genomic Instability Biomarker May Help Predict Treatment Response In Triple Negative Breast Cancer

Melinda L. Telli, M.D.
Assistant Professor of Medicine
Stanford University
Division of Medical Oncology

Stanford, CA 94305-5826

Medical Research: What is the background for this study? What are the main findings?

Response: A major goal of this study was to explore a DNA damaging chemotherapy regimen in patients with newly diagnosed early-stage triple-negative or BRCA1/2 mutation-associated breast cancer. This was based on the hypothesis that these types of tumors are more responsive to DNA damaging therapeutics. A second major goal was to identify predictors of response to this platinum-based therapy among patients with sporadic triple-negative breast cancer (TNBC).

Overall, this study demonstrated that the non-anthracycline and non-taxane neoadjuvant regimen of gemcitabine, carboplatin and iniparib resulted in a 36% pathologic complete response rate (pCR). This compares favorably to pCR rates commonly observed with anthracycline and taxane-based regimens in this group of patients. The response rate was higher among triple-negative breast cancer patients with a germline BRCA1 or BRCA2 mutation (56%).

Given the hypothesis of underlying DNA repair defects in sporadic  http://medicalresearch.com/cancer-_-oncology/breast-cancer/novel-combination-treatment-may-help-some-patients-with-ovarian-and-triple-negative-breast-cancers13888/13888/" rel="nofollow - triple-negative breast cancer , we also evaluated a novel measure of genomic instability to detect the accumulation of changes in the genomic landscape of a tumor attributable to defective homologous recombination DNA repair. Homologous recombination deficiency was assessed by loss of heterozygosity (HRD-LOH) in pretreatment core breast biopsies. Very importantly, we found that the HRD-LOH assay was able to identify patients with sporadic TNBC lacking a BRCA1 or BRCA2 mutation, but with an elevated HRD-LOH score, who achieved a favorable pathologic response.

Medical Research: What should clinicians and patients take away from your report?

Response: Our data do not have a direct impact for clinical practice today, but they strongly suggest that patient selection based on underlying DNA repair deficiency in future randomized trials of standard versus DNA repair defect–targeted therapy in  http://medicalresearch.com/cancer-_-oncology/breast-cancer/breast-cancer-7-triple-negative-subtypes-chemotherapy-response/2180/" rel="nofollow - triple-negative breast cancer  hold great promise. In particular, germline BRCA1 and BRCA2 mutation status, as well as the HRD-LOH assay emerged as important biomarkers associated with improved neoadjuvant response to this platinum-based regimen.

Medical Research: What recommendations do you have for future research as a result of this study?

Response: At present, three phase II randomized trials have been reported, two of which showed an improvement in pCR rate when carboplatin is added to anthracycline and taxane-based neoadjuvant therapy. Whether this will result in improved long-term outcomes remains unknown. Our data support that future investigation with treatment selection based on tumor DNA repair capacity in  http://medicalresearch.com/cancer-_-oncology/breast-cancer/possible-new-chemotherapy-regimen-for-triple-negative-breast-cancer/13139/" rel="nofollow - triple-negative breast cancer  holds tremendous promise and may be able to identify those patients who stand to gain most from a platinum-based approach.

Citation:

http://jco.ascopubs.org/citmgr?gca=jco%3BJCO.2014.57.0085v1" rel="nofollow - Phase II Study of Gemcitabine, Carboplatin, and Iniparib As Neoadjuvant Therapy for Triple-Negative and  - 2 Mutation–Associated Breast Cancer With Assessment of a Tumor-Based Measure of Genomic Instability: PrECOG 0105

http://jco.ascopubs.org/citmgr?gca=jco%3BJCO.2014.57.0085v1" rel="nofollow - Melinda L. Telli, Kristin C. Jensen, Shaveta Vinayak, Allison W. Kurian, Jafi A. Lipson, Patrick J. Flaherty, Kirsten Timms, Victor Abkevich, Elizabeth A. Schackmann, Irene L. Wapnir, Robert W. Carlson, Pei-Jen Chang, Joseph A. Sparano, Bobbie Head, Lori J. Goldstein, Barbara Haley, Shaker R. Dakhil, Julia E. Reid, Anne-Renee Hartman, Judith Manola, and James M. Ford

http://jco.ascopubs.org/citmgr?gca=jco%3BJCO.2014.57.0085v1" rel="nofollow - JCO JCO.2014.57.0085; published online on April 6, 2015;

http://medicalresearch.com/cancer-_-oncology/breast-cancer/genomic-instability-biomarker-may-help-predict-treatment-response-in-triple-negative-breast-cancer/14160/" rel="nofollow - http://medicalresearch.com/cancer-_-oncology/breast-cancer/genomic-instability-biomarker-may-help-predict-treatment-response-in-triple-negative-breast-cancer/14160/



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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: KristyLee
Date Posted: May 14 2015 at 11:10am
I had carbo and got a PCR.  My team was giving me carbo before my genetic testing, but when I found out that I was brca1+, I was especially glad to be receiving it.  It was a tough drug for me, on par with A/C as far as fatigue, nausea, etc.  The Taxol was much easier to tolerate.  

I'm very glad I received it, though! 


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Dx 09/14 Stage 2 TNBC, Grade 3, 3cm, no nodes. BRCA1+ Neoadjuvant treatment: 4 AC/T, 12 Taxol, 4 Carboplatin. BMX Diep Flap Hyster 3/5/15. Path report PCR, no radiation advised.


Posted By: 123Donna
Date Posted: Jun 15 2015 at 7:43pm
bumping for new members

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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: ImaJ
Date Posted: Aug 22 2015 at 11:08pm
Have any of you had a conversation with your oncologists about Carboplatin only being necessary if you are BRCA positive?  I have seen two oncologists who both say that there is not enough evidence that platinum based drugs increase positive outcome in BRCA negative patients.  I happen to be BRCA negative, and although both oncologists say we can discuss Carboplatin and add it to Taxol if I want to, they don't necessarily recommend it.  


Posted By: 123Donna
Date Posted: Aug 23 2015 at 1:25pm
ImaJ,

I'm BRCA Negative.  When I had my recurrence my onc thought my tumor might have been resistant to taxanes like I had in my initial treatment.  I think some of the platinum chemos work well with basal-like tumors.  So she suggested a clinical trial with Carbo/Gemzar and Iniparib (labeled a parp at the time).  I had a great response to the chemo and was NED after 2 cycles.  Based on my experience, platinum chemos may work well on many of us TNBCers.  The question is which ones?  The study mentioned about might be a key:

Response: Our data do not have a direct impact for clinical practice today, but they strongly suggest that patient selection based on underlying DNA repair deficiency in future randomized trials of standard versus DNA repair defect–targeted therapy in  http://medicalresearch.com/cancer-_-oncology/breast-cancer/breast-cancer-7-triple-negative-subtypes-chemotherapy-response/2180/" rel="nofollow - triple-negative breast cancer  hold great promise. In particular, germline BRCA1 and BRCA2 mutation status, as well as the HRD-LOH assay emerged as important biomarkers associated with improved neoadjuvant response to this platinum-based regimen.

There may not be enough data out there for many oncs to feel comfortable recommending it in the neoadjuvant setting at this time.  My 2 cents?  If I was newly dx the first time, I'd try and throw everything at it and hope it doesn't come back.  

Donna


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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Aug 25 2015 at 8:50am
Dr. Sharma receives research award from ASCO to continue study on triple-negative breast cancer

Dr. Sharma was awarded the 2015 Advanced Clinical Research Award in Breast Cancer from the American Society of Clinical Oncology to continue her research on triple-negative breast cancer detailed below.

How do you treat a cancer that does not have a readily identifiable molecular target?

This is currently the case for triple-negative breast cancer, according to Priyanka Sharma, M.D., member of the Drug Discovery, Delivery and Experimental Therapeutics Program at The University of Kansas Cancer Center, and associate professor of hematology and oncology at the University of Kansas Medical Center. Dr. Sharma is working to identify markers that would improve the treatment of triple-negative breast cancer.

Triple-negative breast cancer is a "waste basket term" because unlike other subtypes of breast cancer which are defined by presence of therapeutic markers, triple negative breast cancer is defined by the absence of therapeutic markers (estrogen receptor, progesterone receptors and HER2 protein). And, as Dr. Sharma puts it, "You can't target something that doesn't exist. We still haven't figured out how to define triple-negative breast cancer by the presence of markers that can turn into valid actionable targets."

Dr. Sharma is looking at what she's calling "BRCAness" or deficiency in DNA damage repair machinery (specifically homologous recombination repair pathway defects) in triple negative breast cancer as a potential prognostic and predictive marker.

Triple negative breast cancer and cancer that arises in patients with heritable germline BRCA1 mutations share several phenotypic and molecular similarities.
While only about 10 to 20 percent of triple-negative breast cancer patients have a germline BRCA mutation, it is believed that 50 to 70 percent of patients with triple-negative breast cancer may harbor BRCAness. BRCA1 and BRCA2 are genes that code for proteins that are vital in repairing DNA breaks through homologous recombination repair mechanism. In people who harbor a heritable germline mutation on BRCA1 or BRCA2, DNA repair is defective and this ultimately leads to breast and other types of cancers.

Similarly, this kind of DNA repair deficiency could happen with germline or somatic alterations (mutations, rearrangements, DNA methylation) in other genes that are involved in DNA repair pathway. Researchers, including Dr. Sharma, believe that those BRCA1 mutation-associated cancers and other cancers that express BRCAness can potentially be treated the same way.

As BRCAness is comprised of many distinct properties, a single test is unlikely to identify BRCAness patients that will benefit from BRCA1-directed therapy. Dr. Sharma is studying a platform of four markers to detect BRCAness that include BRCA1 promoter methylation, homologous recombination deficiency score, BRCA1 expression and tumor infiltrating lymphocytes. Dr. Sharma is using data and specimens from an already completed SWOG clinical trial that utilized standard adjuvant chemotherapy treatment.

By identifying which combination of these markers contributes the most to BRCAness, it would be easier to predict a patient's prognosis and determine specific triple-negative cases that would be at significant risk for recurrence after primary treatment.

Besides finding targetable biomarkers, one of the other challenges with treating triple-negative breast cancer is that chemotherapy treatment options have not changed significantly in the last 10 years, according to Dr. Sharma. Although it is clear that triple negative breast cancer is very different from other  http://www.news-medical.net/health/What-is-Breast-Cancer.aspx" rel="nofollow - types of breast cancer , the current standard is to use the same chemotherapy for all sub-types of breast cancers.

There is now renewed interest, however, in studying Platinum-based chemotherapies in triple negative and BRCA associated breast cancer. Platinum-based chemotherapies (like cisplatin and carboplatin) may be effective for treatment of breast cancers with BRCAness because they bind to DNA and interfere with the cell's repair mechanism, causing it to die.

"This biomarker project would play an important role in identifying triple negative breast cancer patients who might benefit the most from robust DNA damaging agents like platinum compounds and PARP inhibitors," said Dr. Sharma. PARP inhibitors are targeted agents that also impede DNA repair and are currently being studied in treatment of cancers arising in patients with BRCA1 and BRCA2 mutations and in patients with triple negative breast cancer.

The hypothesis that these drugs may be a better treatment option is based off a pilot grant funded by The University of Kansas Cancer Center. Working in collaboration with Andy Godwin, Ph.D., deputy director of The University of Kansas Cancer Center and director of the Biospecimen Repository, and Roy Jensen, M.D., director of The University of Kansas Cancer Center, Dr. Sharma looked at the impact of BRCA promoter methylation, expression and mutations and found that "when BRCAness was present, treatment with a platinum-based chemotherapy was associated with a very good long-term outcome," said Dr. Sharma.

By researching BRCAness markers like BRCA promoter methylation , expression, homologous recombination deficiency, and gene expression patters, Dr. Sharma is hoping she can give a more concrete definition to the BRCAness phenotype in triple-negative breast cancer.

"The key to improving treatment outcomes in triple negative breast cancer is to focus research efforts on biomarkers of response and resistance to standard and novel agents," she said.

http://www.news-medical.net/news/20150825/Dr-Sharma-receives-research-award-from-ASCO-to-continue-study-on-triple-negative-breast-cancer.aspx" rel="nofollow - http://www.news-medical.net/news/20150825/Dr-Sharma-receives-research-award-from-ASCO-to-continue-study-on-triple-negative-breast-cancer.aspx




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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Feb 29 2016 at 7:40am
Researchers Debate Role of Pre-op Carboplatin in TNBC
Findings from GeparSixto and CALGB 40603 trials
http://www.clinicaloncology.com/Breast-Cancer/Article/02-16/Researchers-Debate-Role-of-Pre-op-Carboplatin-in-TNBC/35303" rel="nofollow - http://www.clinicaloncology.com/Breast-Cancer/Article/02-16/Researchers-Debate-Role-of-Pre-op-Carboplatin-in-TNBC/35303




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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: gordon15
Date Posted: Feb 29 2016 at 7:34pm
Thanks for the info, it seems like Carboplatin before surgery is a benefit, according to this study, I focus on the positives...for my wife...


Posted By: 123Donna
Date Posted: Jun 22 2019 at 12:47pm

Neoadjuvant Chemotherapy Considerations in Triple-Negative Breast Cancer


The optimal neoadjuvant chemotherapy (NACT) regimen in triple-negative breast cancer (TNBC) has not been clearly defined. Achieving a pathologic complete response (pCR) provides important prognostic information, and, especially in TNBC, is considered a surrogate endpoint for event-free survival. . .

. . .

Carboplatin is an attractive drug for use in TNBC due to its particular relevance to the pathobiology of TNBC. About 80% of BRCA1 mutation–associated breast cancers are triple-negative, and are generally regarded as particularly sensitive to interstrand cross-linking agents, such as platinum analogs, due to the defect in homologous recombination (HR)-based DNA repair characteristic of a BRCA1 mutation. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865448/#R6" rel="nofollow - 6 Additionally, a subset of TNBC tumors exhibit similar defects in HR-based DNA repair, even in the absence of a germline BRCA mutation, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865448/#R7" rel="nofollow - 7 and these tumors may be carboplatin-sensitive. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865448/#R8" rel="nofollow - 8 Single-agent, platinum-based therapy has had varied success in metastatic TNBC, with prospective studies reporting response rates that vary from 10% to 40%. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865448/#R9" rel="nofollow - 9

More recently, 2 studies have investigated the addition of carboplatin to standard-combination NACT in patients with TNBC. The CALGB 40603 study, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865448/#R10" rel="nofollow - 10 conducted in the United States, was a phase II, 2 × 2 factorial trial that investigated the benefit of adding carboplatin, bevacizumab, or the combination to taxane/anthracycline-based chemotherapy. The trial enrolled 443 women with stage II/III TNBC into 1 of 4 arms. The chemotherapy backbone was 12 weeks of weekly paclitaxel (80 mg/m2), followed by dose-dense doxorubicin and cyclophosphamide (ddAC) every 2 weeks for 4 cycles (60 mg/m2 and 600 mg/m2, respectively), which formed the control group to 3 experimental arms: (1) bevacizumab 10 mg/kg every 2 weeks for 9 cycles; (2) carboplatin area under the curve (AUC) 6 every 3 weeks for 4 cycles; and (3) both bevacizumab and carboplatin, dosed as above. These arms gave the experimental drug(s) concurrently with paclitaxel, with bevacizumab also partially overlapping with the ddAC treatment period.

The addition of carboplatin significantly increased the pCR rate compared with control, from 46% to 60% (OR, 1.76, P = .0018). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865448/#R10" rel="nofollow - 10 While the addition of bevacizumab resulted in a similar pCR rate, the combination of both agents resulted in the numerically highest pCR rate of 67%. However, in the subsequent survival analysis, adding carboplatin did not significantly impact survival. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865448/#R11" rel="nofollow - 11 The absolute benefit in 3-year event-free survival (EFS) of adding carboplatin was 4.9% (76.5% vs 71.6%, respectively; HR, 0.84; 95% CI, 0.58–1.22; P = .36). Overall survival (OS) differences were also not significant, with 81.9% OS in the carboplatin group versus 84.6% without carboplatin (HR, 1.15; 95% CI, 0.74–1.79; P = .53). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865448/#R11" rel="nofollow - 11 Furthermore, toxicity was higher in the carboplatin group, with those who received carboplatin being less likely to complete therapy without skipping doses, requiring a dose modification, or discontinuing therapy early. Grade ≥3 neutropenia and thrombocytopenia were also more common in the carboplatin group (56% and 20%, respectively) as compared with control (22% and 4%, respectively). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865448/#R10" rel="nofollow - 10

These results conflict with those in the Gepar-Sixto trial. In GeparSixto, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865448/#R12" rel="nofollow - 12 a total of 595 patients with centrally confirmed TNBC were enrolled into 2 groups, with both groups receiving 18 weeks of weekly paclitaxel, weekly nonpegylated liposomal doxorubicin, and bevacizumab every 3 weeks. The experimental arm additionally received weekly carboplatin. A total of 333 women completed treatment in the combined arms. In the TNBC subgroup, carboplatin resulted in a significantly improved pCR rate over control (53% vs 37%; P = .005). This translated into an absolute benefit in 3-year EFS for the addition of carboplatin over control of 9.7% (85.8% vs 76.1%, respectively; HR, 0.56 [95% CI, 0.33–0.96]). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865448/#R12" rel="nofollow - 12

Clearly, the outcomes were better in the Gepar-Sixto trial compared with CALGB 40603. However, there are several differences between these 2 studies worth noting. GeparSixto had more-favorable baseline characteristics, as 26% of patients in GeparSixto were cN0, compared with 42% in CALGB 40603. Additionally, a larger proportion were cT1 in GeparSixto (26% vs 11%). The backbone therapy was also more intensive in GeparSixto, although this would be expected to affect all arms. In CALGB 40603, the backbone therapy also included cyclophosphamide, which can also cause DNA damage like platinum agents, potentially making the treatment effect similar in the control and experimental arms. Last, the dosing intervals were more compact in GeparSixto, which would potentially allow for less time for DNA repair. Toxicity was greater in the carboplatin-containing arms of both studies, but more grade 3/4 toxicities were seen in GeparSixto relative to CALGB 40603. There are also no data on the long-term effects of these experimental regimens because the median follow-up time was only 3 years.

With these 2 studies in mind, the decision to add carboplatin to a NACT regimen remains an individualized one. Although the hazard ratios suggest benefit, its small size suggests that many patients do just fine without the addition of carboplatin, and can be spared the toxicity. When considering the addition of carboplatin, the backbone regimen and dosing schedule of carboplatin may be critical to optimal efficacy of the drug. If carboplatin is added, clinicians should be cautious given the unknown long-term effects of the added toxicity.

A recent study also worth noting combines carboplatin with another drug aimed at exploiting HR-based DNA repair deficiencies. The I-SPY 2 investigators conducted a phase II study of the adaptive randomization of adding veliparib and carboplatin to the paclitaxel portion of weekly paclitaxel followed by doxorubicin and cyclophosphamide, with pCR being the primary endpoint. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865448/#R13" rel="nofollow - 13 Veliparib, a potent inhibitor of oral poly(ADP-ribose) polymerase (PARP), was chosen because of preclinical trials showing that it potentiates the antineoplastic effects of carboplatin. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865448/#R14" rel="nofollow - 14 In patients with TNBC, the pCR rate in the experimental arm was 51% versus 26% in the control arm, resulting in a 99% probability of superiority over control, and an 88% probability of success in a phase III clinical trial. The toxicity profile was similar to that in the CALGB 40603 trial. While this combination appears to improve the rate of pCR compared with control, it is impossible to separate the effects of carboplatin and veliparib. Preliminary data from the Brightness Study presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting helps to clarify this issue.

The Brightness Study randomized 634 patients with resectable, early-stage TNBC to neoadjuvantly receive 1 of 3 paclitaxel-AC–containing arms: veliparib with carboplatin, carboplatin, or backbone therapy alone. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865448/#R15" rel="nofollow - 15 There was no difference in pCR rate between the 2 carboplatin-containing groups (53.2% with veliparib/carboplatin vs 57.5% with carboplatin; P = .36), and both carboplatin-containing groups had a higher pCR rate than the control group (31%; P <.001 in both groups). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865448/#R15" rel="nofollow - 15 These data suggest that the benefit seen in the I-SPY 2 trial was primarily due to carboplatin. Survival outcomes for the Brightness Study are still pending.

Additional studies investigating the role of adjuvant platinum-based therapy are currently ongoing. An ECOG-ACRIN study (E1131, https://clinicaltrials.gov/ct2/show/NCT02445391" rel="nofollow - NCT02445391 ) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865448/#R16" rel="nofollow - 16 randomizes patients who have residual TNBC after NACT to 2 arms: cisplatin or carboplatin versus capecitabine. An NRG study (NRG-BR003, https://clinicaltrials.gov/ct2/show/NCT02488967" rel="nofollow - NCT02488967 ), https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865448/#R17" rel="nofollow - 17 though excluding patients who had received prior NACT, is investigating the addition of carboplatin to AC-paclitaxel solely in the adjuvant setting, and may provide further insight into the efficacy of carboplatin in TNBC.



https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865448/" rel="nofollow - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865448/


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DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15




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