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Don't Delay Chemo

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123Donna View Drop Down
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    Posted: Jan 27 2014 at 8:09pm
Breast Cancer: Don't Delay Chemo

Delaying adjuvant chemotherapy for breast cancer more than 60 days significantly increased the odds of premature death and distant metastasis, a review of almost 7,000 cases showed.

As compared with starting adjuvant therapy within 30 days of surgery, initiating chemotherapy at 61 days or later was associated with a 19% increase in the risk of premature death. In the subgroup of patients with stage III disease, the mortality risk increased by 76%. Relapse-free survival (RFS) and distant relapse-free survival (DRFS) worsened regardless of stage at diagnosis, according to Mariana Chavez-MacGregor, MD, of the University of Texas MD Anderson Cancer Center in Houston, and colleagues.

Patients with high-risk breast cancer (triple negative, HER2-positive, or stage III) seemed most susceptible to the adverse effects of delayed chemotherapy, as reported online in theJournal of Clinical Oncology.

"The adverse outcomes occurred when chemotherapy was delayed ≥61 days, which in most circumstances, gives medical oncologists enough time to initiate adjuvant chemotherapy," the authors concluded.

"Among patients with stage II and III breast cancer, triple-negative breast cancer, and HER2-positive tumors, every effort should be made to avoid postponing initiation of adjuvant chemotherapy. This may lead to an improvement in outcomes for these subsets of patients."

Multiple studies have documented survival benefits associated with adjuvant chemotherapy in early breast cancer. Equally well recognized is the heterogeneity of breast cancer, affecting both risk and the benefit of adjuvant chemotherapy.

In most instances, adjuvant chemotherapy begins within a few weeks of surgery. However, the potential impact of a delay in initiation of therapy is unclear, although mathematical models have suggested deleterious effects, in particular, an increased likelihood that treatment-resistant micrometastases would emerge, the authors noted.

Moreover, little information exists relative to the impact of time to chemotherapy on outcomes in different breast cancer subtypes.

In an attempt to fill in some of the information gaps, Chavez-MacGregor and colleagues retrospectively reviewed medical records of 6,827 patients treated for early breast cancer at MD Anderson from 1997 to 2011 and followed for a median duration of 59.3 months.

Patients with stage I-II disease accounted for 84.5% of the study population, and the remaining 15.5% of patients had stage III disease at diagnosis. The study group comprised 2,716 (39.8%) patients who started therapy within 30 days of surgery, 2,994 (43.8%) who initiated adjuvant therapy 31 to 60 days after surgery, and 1,117 (16.4%) who initiated treatment ≥61 days after surgery.

The cohort had a 5-year overall survival (OS) of 84%, 5-year RFS of 69%, and DRFS of 72%. Not unexpectedly, patients with larger tumors and greater nodal involvement had worse OS, RFS, and DRFS, the authors noted.

Analysis of factors that influenced outcomes of interest showed no difference in OS, RFS, or DRFS in patients with hormone receptor-positive or HER2-positive tumors, regardless of when they initiated therapy.

The 5-year OS estimate did differ among HER2-positive patients who received trastuzumab (Herceptin), as better survival was observed in patients who started therapy within 30 days of surgery (88%) compared with 31 to 60 days (87%) or ≥61 days (75%, P=0.01). The difference between ≥61 days and ≤30 days translated into a hazard ratio of 3.09 (95% CI 1.49-6.39).

Similarly, patients with triple-negative breast cancer had a 5-year OS estimate of 70% when they started chemotherapy within 30 days, 59% for therapy starting between 31 and 60 days, and 67% for therapy ≥61 days after surgery (P=0.005). Comparing the latest and earliest initiation times resulted in an HR of 1.54 (95% CI 1.09-2.18).

Neither RFS nor DRFS differed by time to chemotherapy in patients with stage I disease. Among patients with stage II disease, the hazard for DRFS increased by 18% to 20% when chemotherapy was started more than 30 days after surgery.

The subgroup of patients with stage III disease had a 76% increase in mortality risk if they started chemotherapy ≥61 days after surgery versus 30 days or less (HR 1.76, 95% CI 1.26-2.46). Risks associated with RFS and DRFS increased by 34% and 36%, respectively.

The study is consistent with other reports in the literature, said Jim Biagi, MD, of Queen's University in Kingston, Ontario.

"The study adds to the available literature suggesting that delays may be detrimental to a patient's cancer outcome," Biagi told MedPage Today by email. "Indeed, patients who had the highest-risk features for breast cancer recurrence, and who would thus derive the greatest benefit from adjuvant chemotherapy, were the most vulnerable to this effect."

"While discrepancies in their results limit our ability to make a strong statement about delays, the study is an important addition to our understanding of the impact delays might have on patient outcomes. It seems to me that if we are asking our patients to undergo 4 to 6 months of chemotherapy, that we offer the treatment in a timely manner."

Biagi participated in a meta-analysis of studies evaluating the impact of time to chemotherapy on survival in colorectal cancer and found a significant association between increasing time to therapy and worse OS and overall survival and disease-free survival. However, in another study Biagi was involved in, an analysis of time to chemotherapy showed no significant effecton survival in non-small-cell lung cancer.

The study was supported by the National Cancer Institute, Komen for the Cure, American Cancer Society, and the Nelly B. Connally Breast Cancer Research Fund.

http://www.medpagetoday.com/HematologyOncology/BreastCancer/44002

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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Bayside View Drop Down
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Bayside Quote  Post ReplyReply Direct Link To This Post Posted: Jan 29 2014 at 1:00am
This is a bit scary since my wife is starting on Monday which will be day 61, after the Xmas holidays, surgeons being on holiday, changing doctors, and then the PET scan and port surgery.
wife DX IDC TNBC 11/13. Grade 3, Stage 2a. Lumpectomy 12/13. margins clear, 0/2 nodes
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Lillie View Drop Down
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Lillie Quote  Post ReplyReply Direct Link To This Post Posted: Jan 29 2014 at 11:25am
Dear Bayside,
 
I posted on another site about what chemo regimen your wife might want to consider.  Since you are getting a late start, I would consider aggressive treatment.  The ACT is more aggressive than TC.  Also discuss getting dose dense treatments.  It is not a piece of cake, but it is doeable and may make the difference in success or failure. 
I'm trying to encourage your wife to throw everything but the 'kitchen sink' at this TNBC. 
Please feel free to PM me if you wish.
 
God Bless,
Lillie
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 - 11/2015-9 yrs NED
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Post Options Post Options   Thanks (0) Thanks(0)   Quote lilyrose Quote  Post ReplyReply Direct Link To This Post Posted: Mar 24 2014 at 9:32am
Donna,
Thank you for this info. I am 2 weeks post surgery. Am seeing the oncologist this week. I don't know what he will be suggesting for treatment...but chemo scares me. I'm wondering if I should get more than one opinion on chemo and what drug(s) would be best for my situation. I have read many on here talking about 'dose dense'...can someone explain that to me? Thanks.
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Post Options Post Options   Thanks (0) Thanks(0)   Quote petersdraggon Quote  Post ReplyReply Direct Link To This Post Posted: Apr 28 2014 at 7:46pm
My wife's chemo was delayed, was started at day 60 for reason explained other than that is the way they do it.  I wasn't happy about it. Her surgery was in November and chemo was put-off until January.  I talked about going to another hospital but by the time we did and got set-up it would have led to the same or longer time frame.  I sure found out how important it is to educate yourself as very soon as possible after diagnosis.
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Post Options Post Options   Thanks (2) Thanks(2)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Dec 10 2015 at 5:07pm
Delaying chemotherapy in breast cancer patients reduces overall survival, especially for those with triple-negative breast cancer

Postponing the start of adjuvant chemotherapy for more than 90 days following surgery may significantly increase risk of death for breast cancer patients, particularly those with triple-negative breast cancer (TNBC), according to a new study from The University of Texas MD Anderson Cancer Center. Further, the researchers found that factors such as socio-economic status, insurance coverage and ethnicity were associated with delayed treatment.

According to the study, published in JAMA Oncology, patients who start chemotherapy more than 90 days after surgery are 34 percent more likely to die within five years. Patients with TNBC who delay treatment have a 53 percent increased risk of death.

Adjuvant chemotherapy, which is given after primary surgery, has been demonstrated to benefit patients by decreasing the risk of recurrence and death, explained Mariana Chavez Mac Gregor, M.D., assistant professor, Health Services Research and Breast Medical Oncology. However, delaying the start of adjuvant chemotherapy may allow small remnants of the tumor to grow or become drug-resistant.

Currently, there are no guidelines recommending the optimal time to initiation of adjuvant chemotherapy. The Centers for Medicare & Medicaid Services (CMS) considers the administration of adjuvant chemotherapy within 120 days of diagnosis for certain patients as a quality metric. Eleven cancer hospitals, including MD Anderson, are now reporting on this metric.

Past studies have suggested that delaying the initiation of therapy could result in adverse patient outcomes, but the optimal timing for starting adjuvant therapy has not been defined. To clarify this time frame relative to modern treatments and identify factors contributing to delayed treatment, the researchers analyzed data from the California Cancer Registry.

This population-based study examined data from 24,823 patients with Stage I to III invasive breast cancer diagnosed between January 1, 2005 and December 31, 2010 and treated with adjuvant chemotherapy. This is the largest study investigating the effects of delayed chemotherapy initiation with contemporary treatment regimens.

"Compared to patients starting chemotherapy in the first month after surgery, we observed that those who initiated chemotherapy between 30 and 90 days following surgery did not have adverse outcomes," said Chavez Mac Gregor, lead author of the study. "However, starting chemotherapy more than 90 days after surgery was associated with a statistically significant increase in the risk of death and breast cancer-specific death."

Those patients who started chemotherapy more than 90 days after surgery, represented by 9.8 percent of those included in the study, were 34 percent more likely to die within five years and 27 percent more likely to die from breast cancer in that time frame compared to patients who had surgery within 30 days from surgery.

As the data also included information on breast cancer subtype, the researchers analyzed whether delayed chemotherapy had a differential effect according to disease subtype. For patients with TNBC, a delay of more than 90 days was associated with a 53 percent increase in the risk of death. There was no significant effect from delay for those with hormone-receptor-positive or HER2-positive breast cancers.

"These data suggest that timely initiation of chemotherapy is particularly important among patients with triple-negative breast cancer," said senior author Sharon Giordano, M.D., professor and chair, Health Services Research and professor, Breast Medical Oncology.

This study also sought to determine factors contributing to delayed administration of chemotherapy in order to identify patient groups in need of improved care delivery. While patients with later stage disease and TNBC were less likely to experience delays, increased age, reconstructive surgery and certain socio-demographic factors were associated with postponed treatment.

"We observed, not surprisingly, that socio-demographic factors determined, in great part, some of this delay. Patients with low socio-economic status (SES), those without private insurance and those of Hispanic or African-American descent were more likely to have delays in their treatment," said Chavez Mac Gregor.

Worse overall survival was also associated with patients of African-American descent, lower SES and those with Medicare and Medicaid coverage. In contrast, those patients receiving care at National Cancer Institute-designated cancer centers had a 34 percent lower risk of death compared to those who were treated elsewhere.

"We need to identify the determinants of delays in treatment so we can act on them and potentially improve the delivery of care in vulnerable populations. In most clinical scenarios, administering chemotherapy within three months is more than feasible," said Chavez Mac Gregor.

The results of the current study support including time to chemotherapy initiation as a quality metric, and additionally suggest that treatment should begin within 90 days of surgery, explained Chavez Mac Gregor.

While the authors acknowledge the study may be limited by its retrospective nature, they conclude that all breast cancer patients receiving adjuvant chemotherapy should do so within 90 days of surgery or 120 days of diagnosis.

"We need to start chemotherapy in a timely manner," said Chavez Mac Gregor. "In those patients who want to delay their chemotherapy, I share this data and let them know that a delay can dilute the benefits of treatment. If at all possible, we should not delay."

http://www.eurekalert.org/pub_releases/2015-12/uotm-dci120915.php

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 (1) Thanks(1)   Quote Lillie Quote  Post ReplyReply Direct Link To This Post Posted: Dec 10 2015 at 8:22pm
Thanks for this article Donna.  It carries a really important message, especially for all TN sisters.
 
God Bless,
Lillie
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 - 11/2015-9 yrs NED
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Post Options Post Options   Thanks (1) Thanks(1)   Quote petersdraggon Quote  Post ReplyReply Direct Link To This Post Posted: Dec 16 2015 at 1:31pm
I'd read about this in late November 2013 when my wife was having her operation for tnbc and I pushed to not delay the start of chemo,  so we started immediately after Christmas. I am happy to report she just passed her 2-year anniversary and doing quite well aside from mild lymphodema after a stage 3b diagnosis and having breast conservation surgery. To me it appears to be common sense and shouldn't take years ticking by before it becomes the prescribed treatment when we're dealing with someone's life.  There ought to be a law that dictates they start the chemo as soon as possible regardless of social-economic-insurance status. 
Thanks for the post and getting the word out there!
Greg.
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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: May 01 2016 at 11:41pm
Bump
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: Jul 15 2017 at 1:09pm
bump
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 SusaninVA Quote  Post ReplyReply Direct Link To This Post Posted: Jul 15 2017 at 4:07pm
I remember hanging my head in frustration because my surgeon was insisting on doing a 3rd surgery and would not release me to start chemo.  Everything I was reading here and on other sites emphasized starting chemo ASAP for Triple Negative.  My Nurse Practitioner took my concerns seriously and talked to the surgeon.  Thankfully, he relented and I did meet this deadline.  (While taking the chemo, I requested to talk with my Radiation doctor for his opinion on the 3rd surgery, and he was able to use boosts of radiation to the site of concern and saved me from that surgery.)  If you live in Virginia, you may have met him.  He is Dr. Arthur out of Virginia Commonwealth Univ. and is now chairman of Radiology at VCU.  Unfortunately, that means he no longer carries a patient load, but I imagine he still consults with his physicians.
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Meadow Quote  Post ReplyReply Direct Link To This Post Posted: Oct 10 2017 at 4:01am
My cousin and I were the same - same age, same stage, same treatment. She delayed treatment for personal and insurance reasons and started chemo 4 months after diagnosis. I had surgery 3 weeks after diagnosis and started chemo three weeks after that. My doctors really pushed me to be aggressive, probably based on the quoted studies. I even delayed port placement so I could get going with AC (I had port surgery in between the first and second AC infusions).   My cousin had a recurrence and passed away in 2012. I am fine, with enough years behind me to be confident I am 100% cured. It's just one story, not statistically significant. But I always wonder if my cousin would be celebrating with me if she'd gotten treatment sooner. Thanks for bumping this discussion. I hope it makes a positive difference for our TNBC sisters who are facing treatment.
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Post Options Post Options   Thanks (0) Thanks(0)   Quote SusaninVA Quote  Post ReplyReply Direct Link To This Post Posted: Oct 11 2017 at 1:24pm
Meadow, Thank You for sharing your story on this.  I personally think that 4 months could make a difference in something that grows as quickly as TNBC.  I'm sorry you lost your cousin.  I'm glad your doctors encouraged you to treat this aggressively.  All cancer is serious, but TNBC seems to have a shorter window of time in which treatment can make a such a difference.  

Edited by SusaninVA - Oct 11 2017 at 2:12pm
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