HER2-like And Basal-Like Genotype Breast Cancer Are More Likely To Respond To Chemotherapy

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Main Category: Breast Cancer
Also Included In: Cancer / Oncology;  Clinical Trials / Drug Trials
Article Date: 26 Dec 2009 - 3:00 PDT

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New data suggest that breast cancer patients with HER2- and basal-molecular subtypes are more likely to respond to neoadjuvant chemotherapy than patients with luminal-type molecular subtype characteristics.

The findings were released at the 32nd Annual San Antonio Breast Cancer Symposium (SABCS).

George Somlo, MD, Co-Director of the Breast Cancer Program at the City of Hope Comprehensive Cancer Center in Duarte, California, and colleagues are assessing the predictive value of Mammaprint scores as well as basal-, luminal-, and HER2- molecular subtype profiling in women with stages II to III and inflammatory breast cancer in order to determine the response to treatment for three different neoadjuvant chemotherapy regimens.

These regimens include docetaxel, doxorubicin, cyclophosphamide (TAC); doxurubicin, cyclophosphamide, and nab--paclitaxel; and carboplatin with or without trastuzumab.

Prior research has shown that pathologic complete response and minimal residual cancer burden after neoadjuvant chemotherapy may predict improved survival, Dr. Somlo and his group wrote in their poster presentation. Thus, improved neoadjuvant chemotherapy regimens in conjunction with molecular markers that predict for both response and/or resistance are needed.

For the ongoing trial, women with stages II-III breast cancer are randomized to receive 6 cycles of docetaxel 75 mg/m2, doxorubicin 50 mg/m2, cyclophosphamide 500 mg/m2 with filgrastim support (TAC, arm A) versus a novel regimen of A 60 mg/m2 and C 600 mg/m2 given every 2 weeks x 4, followed by 3 weekly doses of carboplatin (AUC 2) and nab-paclitaxel 100 mg/m2 repeated as 28 day cycles x 3 (arm B). Patients with HER2 + BC receive neoadjuvant chemotherapy similar to arm B, but with the addition of 12 weekly doses of trastuzumab given together with carboplatin and nab-paclitaxel (arm C).

Sufficient amounts of breast cancer tissue and good quality RNA for gene array assessment were procured in 64% of the first 90 patients who have undergone pre-treatment core biopsies followed by neoadjuvant chemotherapy and then definitive surgery.

Complete data available in 50 women thusfar reveal that by gene profiling, 28% of the tumors were HER2-type (versus 38% by IHC 3+, or FISH, representing all patients treated on arm C), 26% basal-type, 42% luminal-type, and 4% borderline luminal-type. Poor-prognosis signature by the 70-gene assay was observed in 74% of patients: 92% of HER2-type, 100% of basal-type, and 52% of luminal-type tumors were characterized as poor-risk by the 70-gene assay.

Following neoadjuvant chemotherapy, Symmans RCB scores of 0-1 were documented in 71% of patients with HER2-like, 38% with basal-type, and 28% of patients with luminal-type molecular subtype characteristics.

Overall, the results to date suggest that breast cancer with HER2- and basal-molecular subtypes are more likely to respond to neoadjuvant chemotherapy and are frequently associated with poor-risk characteristics as determined by the 70-gene assay, Dr. Somlo said.

He added that the trial plans to recruit a total of 115 women.

Written by Jill Stein
Jill Stein is a Paris-based freelance medical writer.
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