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Adding Carboplatin Increases PCR

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Post Options Post Options   Thanks (0) Thanks(0)   Quote rosewater Quote  Post ReplyReply Direct Link To This Post 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
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+
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Post Options Post Options   Thanks (0) Thanks(0)   Quote tmariee Quote  Post ReplyReply Direct Link To This Post 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
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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Aug 09 2014 at 12:30pm
Bumping for new members
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)
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Post Options Post Options   Thanks (0) Thanks(0)   Quote rosewater Quote  Post ReplyReply Direct Link To This Post 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
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+
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Post Options Post Options   Thanks (0) Thanks(0)   Quote rosewater Quote  Post ReplyReply Direct Link To This Post 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
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+
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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Dec 12 2014 at 10:40pm
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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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post 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, Eric Winer, MD, director of Breast Oncology at the 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

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)
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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post 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."

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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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: May 12 2015 at 6:39pm
bumping for new members

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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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: May 12 2015 at 6:48pm
Optimizing Chemotherapy in Triple-Negative Breast Cancer: The Role of Platinum



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)
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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post 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 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 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 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:

Phase II Study of Gemcitabine, Carboplatin, and Iniparib As Neoadjuvant Therapy for Triple-Negative and BRCA1/2 Mutation–Associated Breast Cancer With Assessment of a Tumor-Based Measure of Genomic Instability: PrECOG 0105

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

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/

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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Post Options Post Options   Thanks (0) Thanks(0)   Quote KristyLee Quote  Post ReplyReply Direct Link To This Post 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! 
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.
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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Jun 15 2015 at 7:43pm
bumping for new members
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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Post Options Post Options   Thanks (0) Thanks(0)   Quote ImaJ Quote  Post ReplyReply Direct Link To This Post 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.  
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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post 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 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


Edited by 123Donna - Aug 23 2015 at 1:27pm
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)
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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post 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 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


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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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Feb 29 2016 at 7:40am
Researchers Debate Role of Pre-op Carboplatin in TNBC
Findings from GeparSixto and CALGB 40603 trials


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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Post Options Post Options   Thanks (0) Thanks(0)   Quote gordon15 Quote  Post ReplyReply Direct Link To This Post 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...
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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post 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.6 Additionally, a subset of TNBC tumors exhibit similar defects in HR-based DNA repair, even in the absence of a germline BRCA mutation,7 and these tumors may be carboplatin-sensitive.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%.9

More recently, 2 studies have investigated the addition of carboplatin to standard-combination NACT in patients with TNBC. The CALGB 40603 study,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).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.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).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).10

These results conflict with those in the Gepar-Sixto trial. In GeparSixto,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]).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.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.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.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).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, NCT02445391)16 randomizes patients who have residual TNBC after NACT to 2 arms: cisplatin or carboplatin versus capecitabine. An NRG study (NRG-BR003, NCT02488967),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.



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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