New Data on Neoadjuvant Chemo and Breast Cancer Recurrence

Nick Mulcahy

September 05, 2014

Women with breast cancer who respond well to neoadjuvant chemotherapy could be spared radiotherapy after surgery, and might also need less extensive surgery.

That's a hope that stems from a meta-analysis of clinical trial data involving nearly 12,000 women. This is the largest study of its kind to date, but more data are needed to inform guidelines before any changes to practice can be recommended, cautioned the lead investigator Eleftherios Mamounas, MD, MPH, professor of surgery at the University of Central Florida in Orlando.

The investigators found that in women with breast cancer treated with neoadjuvant chemotherapy, pathologic complete response (pCR) and tumor subtype are "strong predictors" of local and regional breast cancer recurrence.

Identifying independent predictors of recurrence is important because the information "can potentially change the management of the patient," Dr. Mamounas explained.

He was speaking at a presscast held in advance of the 2014 Breast Cancer Symposium in San Francisco, where the study will be presented.

Dr. Mamounas was referring to an evolving issue in breast cancer: choosing patients who are optimal candidates to forgo additional treatment after surgery, which, in this case, is most likely to be radiation therapy.

The idea is that patients with characteristics that would minimize the risk for recurrence after neoadjuvant chemotherapy would be candidates for skipping radiation. In addition, a complete response to neoadjuvant chemotherapy could possibly reduce the need for mastectomy and lymph node removal.

The issue has become more pressing, suggested Dr. Mamounas, because various studies indicate that neoadjuvant and adjuvant chemotherapy have a similar effect on outcomes in breast cancer.

The advantage of neoadjuvant chemotherapy is that if clinicians can use information specific to that approach, such as pCR, they can identify patients who can safely proceed without radiation.

Largest Study of Its Kind

Dr. Mamounas and his colleagues from an international collaboration, known as CTNeoBC, reviewed 12 large clinical trials of neoadjuvant chemotherapy in women with stage I to III breast cancer, which included 11,955 patients with pCR data and a median follow-up of 5.4 years.

The team conducted a multivariate analysis to identify independent predictors of locoregional recurrence (LRR) and assessed LRR rates using various clinic-pathologic factors, such as pCR and breast cancer subtype.

The overall 5-year rate of LRR was "low" (8.3%), Dr. Mamounas reported. However, LLR rates differed by tumor subtype, he said.

Table. 5-Year Risk for LRR by Tumor Subtype

Tumor Subtype Risk for LRR, %
Triple negative 12.2
HER2-negative  
   Hormone-receptor positive, grade 1/2 4.2
   Hormone-receptor positive, grade 3 9.2
HER2-positive  
   Hormone-receptor positive 9.7
   Hormone-receptor negative 14.8

 

Age was found to be an independent predictor of LRR in patients who had undergone lumpectomy but not in those who had undergone mastectomy. Specifically, compared with older patients, lumpectomy patients younger than 50 years had a hazard ratio of 1.41 (nominal P = .007).

A pCR in the breast and pathologic axillary nodal status were also independent predictors of LRR for both mastectomy and lumpectomy patients, Dr. Mamounas reported. However, breast cancer subtypes are independent predictors of LRR even when pathologic response is taken into account, he explained.

The results are a "very complicated matrix," said presscast moderator Harold J. Burstein, MD, PhD, from Harvard Medical School in Boston, who was not involved in the study.

This is an "inside baseball" study, he said, using a popular phrase from the American vernacular that describes an esoteric matter.

One of the great hopes for the data is that they will be used to support ongoing clinical trials that are "attempting to tailor" LRR in this setting, said Dr. Mamounas.

Dr. Mamounas reports financial relationships with Genomic Health, GE Healthcare, Celgene, Pfizer, Eisai, and Genentech/Roche. Some of his coauthors also report multiple financial relationships. Dr. Burstein has disclosed no relevant financial relationships.

2104 Breast Cancer Symposium (BCS): Abstract 61. Presented September 4, 2014.

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