Identifying human epidermal growth factor receptor (HER)2 pathway cancer “addicts,” omitting adjuvant chemotherapy based on a 21-gene Recurrence Score (RS), and improving survival with dose-dense chemotherapy in premenopausal breast cancer were among the treatment topics highlighted during the 10th European Breast Cancer Conference (EBCC-10) in Amsterdam, the Netherlands.

Preoperative Lapatinib + Trastuzumab Reduces, Eliminates Tumors

One of the most widely covered presentations was the finding that after only 11 days from date of diagnosis, treatment with the anti-HER2 preoperative combination of lapatinib and trastuzumab significantly reduced or eliminated tumors in approximately 25% of women with operable breast cancer, offering the “potential to personalize therapy for these patients” by identifying “cancers addicted to the HER2 pathway,” the study authors noted.1

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“This has ground-breaking potential because it allows us to identify a group of patients who, within 11 days, have had their tumors disappear with anti-HER2 therapy alone and who potentially may not require subsequent chemotherapy,” Nigel Bundred, MD, professor of surgical oncology at The University of Manchester and the University Hospital of South Manchester NHS Foundation Trust, Manchester, United Kingdom, stated.2

Responding to media coverage, the lead investigators released a statement noting that “while we do not wish to downplay the significance of the findings, we also urge caution in their interpretation.” Specifically, not only is there no evidence to date that this combination would be effective in any other tumors, but the effect of treatment on long-term survival remains unknown.3

The multicenter, 2-part, randomized UK EPHOS-B trial was designed to measure the effect of 10 to 12 days of preoperative anti-HER2 therapy on proliferation and apoptosis in treatment-naive HER2-positive breast cancer. The study recruited 257 women; in part 1, 130 patients were randomized to no perioperative treatment (control), lapatinib only, and trastuzumab only. Following reports of the efficacy of the combination of lapatinib and trastuzumab to treat HER2-positive breast cancer, the study was amended so that in part 2, the subsequent 127 women were randomized to control, trastuzumab only, or the combination of lapatinib and trastuzumab.

Median age was 52 years, 48% had tumors greater than 2 cm, and 51% were biopsy grade 3 at study entry; 67% were estrogen-receptor positive and 40%, progesterone-receptor positive.

Tumor tissue samples taken at diagnosis and during surgery were analyzed for levels of Ki67 protein and pathology reports reviewed.

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In addition to a decrease in Ki67 levels, among women who had received the combination therapy, 10.6% had a pathological complete response (pCR) and 16.7%, minimal residual disease (MRD), defined as a tumor less than 5 mm in diameter. In contrast, women who had received trastuzumab only had a pCR of 0% and an MRD of 3.1%. In the control group, no women had either a pCR or an MRD.