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Women with luminal A breast cancer derive no benefit from adjuvant chemotherapy
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SAN ANTONIO — Adjuvant chemotherapy conferred no long-term DFS benefit to premenopausal women with invasive luminal A breast cancer, according to a prospective–retrospective analysis presented at San Antonio Breast Cancer Symposium.
Luminal A is a common breast cancer subtype typically associated with more favorable prognosis, better survival and lower risk for recurrence than other subtypes.
Torsten Nielsen
Prior research suggested intrinsic breast cancer subtypes respond differently to various types of chemotherapy. However, most of this evidence is from in vitro, animal or cohort studies, according to Torsten Nielsen, MD, PhD, professor of pathology at University of British Columbia.
“We really needed randomized clinical trials to look at these findings, particularly with really stringent statistical analysis, but it has been very hard to do these studies,” Nielsen said during a press conference. “The question was settled in the 1980s that adjuvant chemotherapy helps women with breast cancer, and since that time it has been unethical to randomize women in most settings to no chemotherapy.”
To determine the predictive value of intrinsic breast cancer subtypes with regard to adjuvant chemotherapy response, Nielsen and colleagues analyzed tissue samples from participants in the Dutch Breast Cancer Cooperative Group (DBCG) 77B trial.
That trial, initiated in 1977, included 1,146 premenopausal women with lymph node-positive invasive breast cancer whose tumors were larger than 5 cm. All women received radiotherapy. None received endocrine therapy, but they did receive mastectomy supported by axillary node dissection and chest wall radiation.
Researchers in the DBCG 77B trial randomly assigned women to one of four study arms. Women in two study arms received adjuvant chemotherapy — either cyclophosphamide alone or cyclophosphamide with methotrexate and fluorouracil. Women in the other two arms received no adjuvant chemotherapy.
Ten-year DFS served as the primary endpoint. Results demonstrated a clear advantage for chemotherapy in the adjuvant setting (HR = 0.63; 95% CI, 0.49-0.81).
“This material led us to address the question we had really been wondering about: Do luminal A tumors — the low-risk intrinsic subtype — derive any benefit from chemotherapy?” Nielsen said.
Nielsen and colleagues analyzed tissue samples from 709 participants in the 77B trial for the presence of ER, PR, HER-2 and Ki67. The final study set included results from 633 samples, a little more than one-quarter of whom had luminal A disease.
Results of multivariate Cox proportional hazards model analysis showed women with non-luminal A breast cancer derived a significant 10-year invasive DFS benefit with chemotherapy (HR = 0.5; 95% CI, 0.38-0.66), but women with luminal A subtype did not (HR = 1.07; 95% CI, 0.53-2.14). Researchers determined the heterogeneity was statistically significant (P < .05).
Nielsen and colleagues observed a similar trend for 25-year OS; however, the effect did not reach statistical significance.
The researchers acknowledged several limitations to their study. The immunohistochemistry method they used has limited analytical validity as a clinical test, and only tissue microarrays were used. Also, the DBCG 77B is an older trial in which women did not receive endocrine therapy, anti–HER-2 therapy, or anthracyclines and taxanes, so its relevance to current patient populations must be considered, Nielsen said.
“Women with this common luminal A subtype get no benefit from chemotherapy, even if node-positive and even in the absence of hormonal therapy,” Nielsen concluded. “Given [these results], it would certainly be expected that women with similar tumor characteristics getting endocrine therapy would also receive no benefit from chemotherapy.” – by Mark Leiser
Reference:
Nielsen TO, et al. Abstract S1-08. Presented at: San Antonio Breast Cancer Symposium; Dec. 8-12, 2015; San Antonio.
Disclosure: The researchers report ownership interest in Bioclassifier LLC. They also report royalties and other fees from, as well as patents, contracted research and consultant roles with Nanostring Technologies.