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Neoadjuvant chemotherapy response predicted locoregional breast cancer recurrence
Tumor subtype and patients’ pathologic response to neoadjuvant chemotherapy strongly predicted locoregional breast cancer recurrence, according to results of a pooled analysis presented at the Breast Cancer Symposium.
These two factors could be more useful than tumor staging at diagnosis when determining risk for recurrence, researchers wrote.
Eleftherios P. Mamounas
“There is limited information on the rates of locoregional recurrence in patients treated with neoadjuvant chemotherapy, and we know that achieving pathologic complete response with neoadjuvant chemotherapy and having different breast cancer subtypes has been shown to independently predict rates of locoregional recurrence,” researcher Eleftherios P. Mamounas, MD, MPH, FACS, medical director of the Comprehensive Breast Program at University of Florida Health Cancer Center, said during a press conference. “However, we don’t know for sure the combined effect of pathologic complete response and breast cancer subtypes on the rates of locoregional recurrence in patients treated with neoadjuvant chemotherapy.”
The analysis included 11,995 women with stage I to stage III breast cancer who received neoadjuvant chemotherapy. Mamounas and colleagues evaluated locoregional recurrence rates, as well as pathologic complete response, EFS and OS.
At median follow-up of 5.4 years, patients who did not exhibit a pathologic complete response following neoadjuvant chemotherapy were at increased risk for locoregional recurrence compared with those who achieved pathologic complete response.
Patients with residual disease in the breast and no cancerous axillary lymph nodes demonstrated a 1.6-fold increased risk for locoregional recurrence compared with those who achieved pathologic complete response. Patients with cancerous axillary lymph nodes demonstrated a 2.8-fold increased risk for recurrence.
Locoregional recurrence rates varied by tumor subtype. Researchers reported 5-year locoregional recurrence risks of 4.2% for women with HR-positive, HER-2–negative breast cancer with grade 1 or grade 2 tumors; 9.2% for patients with HR-positive, HER-2–negative grade 3 breast cancer; 9.7% for those with HR-positive, HER-2–positive breast cancer; 14.8% for women with HR-negative, HER-2–positive breast cancer; and 12.2% for those with triple-negative breast cancer.
Results of a multivariate analysis indicated age was an independent predictor for recurrence among patients who underwent lumpectomy, but not among those who underwent mastectomy. For both surgery groups, tumor subtype and pathologic complete response status were independent predictors for recurrence.
“We’re finding that receiving neoadjuvant chemotherapy is not only a good option for treating breast cancer and preventing future recurrence in other parts of the body, but it also provides important information on the risk for locoregional recurrence,” Mamounas said in a press release. “This can potentially help to better identify patients at higher risk for recurrence who may benefit from the addition of radiotherapy and those at low risk who may not need it. [Although] more research is needed to inform new practice guidelines based on these insights, the findings provide additional information for doctors and patients to consider when trying to decide on the best locoregional treatment options after neoadjuvant chemotherapy.”
For more information:
Mamounas E. Abstract #61. Scheduled for presentation at: Breast Cancer Symposium; Sept. 4-6, 2014; San Francisco.
Disclosure: The study was funded by Collaborative Trials in Neoadjuvant Breast Cancer. The researchers report research funding, honoraria or other remuneration from, consultant or advisory roles with, stock ownership in and speakers’ bureau roles with AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Celgene, Eisai, Genentech/Roche, Genomic Health, German Breast Group Research GmbH, GlaxoSmithKline, NIH, Novartis, Pfizer, Puma and Teva.
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The data also point to the idea that breast cancer subtype is very important for predicting outcomes.
Early in the modern era, so much of what we’re thinking about in the way of managing breast cancer is driven by understanding these major clinical subtypes. These data really speak to a very complicated matrix that helps us understand the risk for recurrence in a woman who has greater-than-average risk of breast cancer by factoring in the type of breast cancer, the response with upfront chemotherapy and the age of the patient. These multiplexed kinds of information set the stage for a variety of trials that are looking to tailor additional therapy for women who are at higher risk and conversely sparing women who are at lower risk the need for extra treatment, in this case radiation therapy. It’s a bit of insider baseball in the sense that these are the data that really resonate with radiation oncologists, surgeons and medical oncologists, who are into the nitty gritty of caring for women with breast cancer. But for those insiders, these are very helpful data for figuring out who is going to need more therapy and who can be spared additional therapy.
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Several important trends come out of this study. One is that pathologic complete response, either in the nodes or the breast itself, is predictive for locoregional recurrence and may help guide us about whether patients require additional locoregional treatment — for instance, radiotherapy after mastectomy — or the extent of that treatment.
The other important observation was the importance of breast cancer subtype and grade in certain patient subsets. Patients with ER-positive, PR-positive, HER-2–negative low-grade lesions had a very low risk for locoregional recurrence — particularly after mastectomy — when they either had response in the nodes or the breast, demonstrating that these patients can be spared post-mastectomy radiotherapy.
However, these are all retrospective observations, and it will be important to have prospective clinical trials to confirm this given the benefit of post-mastectomy radiation therapy in many patient subsets.