Distinct triple-positive subtypes identified in breast cancer

CHICAGO, IL—Functional subtyping with a multigene classifier resulted in 1 in 5 tumors being reclassified compared with conventional immunohistochemistry/fluorescent in situ hybridization (IHC/FISH) analysis. This study was presented at the 2015 American Society for Clinical Oncology (ASCO) Annual Meeting.

Classifying tumors into molecular subtypes is important to select therapy for patients with breast cancer, as the study's background information explained. Breast cancer subtypes, which include HER2-type, basal-type, luminal A-type, and luminal-B type, are known to have distinct clinical outcomes.

This analysis of the prospective Neoadjuvant Breast Registry Symphony Trial (NBRST) sought to compare a multigene classifier to conventional local IHC/FISH subtyping to predict chemosensitivity. The study defined chemosensitivity as pathological complete response.

Among the 889 study participants, 66 (7%) were stage I, 588 (66%) were stage II, and 234 (26%) were stage III. Hormone receptor status by IHC was positive for 581 patients (65%) and negative for 308 patients (35%). By IHC analysis, 211 patients (23%) were triple-negative, meaning they were negative for estrogen receptor (ER), progesterone receptor (PR), and HER2. HER2 status by IHC/FISH was negative for 629 patients (71%) and positive for 260 patients (29%).

When tested by MammaPrint/BluePrint, 201 of 889 patients (23%) were classified into a different subgroup compared with conventional IHC/FISH assessments.

Among 167 patients classified as HER2-positive and estrogen-receptor-positive by IHC/FISH, 82 (49%) were classified as luminal molecular subtype by BluePrint. Tumors of the luminal subtype of breast cancer are relatively resistant to neoadjuvant chemotherapy and trastuzumab. However, treatment with pertuzumab overcame resistance to neoadjuvant chemotherapy and trastuzumab among many of the patients in the luminal subgroup, as indicated by the pathological complete response rate of 38% (12 of 32 patients) with trastuzumab and pertuzumab treatment versus 4% (2 of 48 patients) with trastuzumab treatment alone among patients who were luminal-type by BluePrint and HER2-positive by IHC/FISH.

Also, 72 (43%) of the patients who were HER2-positive and estrogen-receptor-positive by IHC/FISH were classified as HER2 subtype by BluePrint, and their pathological complete response rate was 59%. Finally, 13 (8%) of the patients who were HER2-positive and estrogen-receptor-positive by IHC/FISH were classified as basal subtype by BluePrint, and their pathological complete response rate was not improved by adding pertuzumab to trastuzumab (38%; 3 of 8 patients) compared with trastuzumab alone (47%; 13 of 26 patients).

The study noted that combining trastuzumab and pertuzumab for dual HER2-inhibition improved pathological complete response rates in all patients, except patients classified as basal-type by BluePrint and as HER2-positive/ER-negative by IHC/FISH.

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