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Clinical Trial
. 2017 Mar;24(3):669-675.
doi: 10.1245/s10434-016-5600-x. Epub 2016 Oct 21.

Chemosensitivity and Endocrine Sensitivity in Clinical Luminal Breast Cancer Patients in the Prospective Neoadjuvant Breast Registry Symphony Trial (NBRST) Predicted by Molecular Subtyping

Pat Whitworth  1 , Peter Beitsch  2 , Angela Mislowsky  3 , James V Pellicane  4 , Charles Nash  5 , Mary Murray  6 , Laura A Lee  7 , Carrie L Dul  8 , Michael Rotkis  9 , Paul Baron  10 , Lisette Stork-Sloots  11 , Femke A de Snoo  11 , Jennifer Beatty  12
Affiliations
Clinical Trial

Chemosensitivity and Endocrine Sensitivity in Clinical Luminal Breast Cancer Patients in the Prospective Neoadjuvant Breast Registry Symphony Trial (NBRST) Predicted by Molecular Subtyping

Pat Whitworth et al. Ann Surg Oncol. 2017 Mar.

Abstract

Purpose: Hormone receptor-positive (HR+) tumors have heterogeneous biology and present a challenge for determining optimal treatment. In the Neoadjuvant Breast Registry Symphony Trial (NBRST) patients were classified according to MammaPrint/BluePrint subtyping to provide insight into the response to neoadjuvant endocrine therapy (NET) or neoadjuvant chemotherapy (NCT).

Objective: The purpose of this predefined substudy was to compare MammaPrint/BluePrint with conventional 'clinical' immunohistochemistry/fluorescence in situ hybridization (IHC/FISH) subtyping in 'clinical luminal' [HR+/human epidermal growth factor receptor 2-negative (HER2-)] breast cancer patients to predict treatment sensitivity.

Methods: NBRST IHC/FISH HR+/HER2- breast cancer patients (n = 474) were classified into four molecular subgroups by MammaPrint/BluePrint subtyping: Luminal A, Luminal B, HER2, and Basal type. Pathological complete response (pCR) rates were compared with conventional IHC/FISH subtype.

Results: The overall pCR rate for 'clinical luminal' patients to NCT was 11 %; however, 87 of these 474 patients were reclassified as Basal type by BluePrint, with a high pCR rate of 32 %. The MammaPrint index was highly associated with the likelihood of pCR (p < 0.001). Fifty-three patients with BluePrint Luminal tumors received NET with an aromatase inhibitor and 36 (68 %) had a clinical response.

Conclusions: With BluePrint subtyping, 18 % of clinical 'luminal' patients are classified in a different subgroup, compared with conventional assessment, and these patients have a significantly higher response rate to NCT compared with BluePrint Luminal patients. MammaPrint/BluePrint subtyping can help allocate effective treatment to appropriate patients. In addition, accurate identification of subtype biology is important in the interpretation of neoadjuvant treatment response since lack of pCR in luminal patients does not portend the worse prognosis associated with residual disease in Basal and HER2 subtypes.

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Figures

Fig. 1
Fig. 1
Probability of pCR (ypT0/isN0) to NCT for the MammaPrint index (n = 405), and probability of pCR as a function of the MammaPrint index. The red and grey circles represent patients who did and did not have a pCR, respectively. The MammaPrint index is positively associated with the likelihood of pCR (p < 0.001), suggesting that patients who are at the highest risk of recurrence are more likely to have chemotherapy benefit. pCR pathological complete response, NCT neoadjuvant chemotherapy
Fig. 2
Fig. 2
Chemosensitivity (pCR) per subtype classification (n = 403). One patient was classified as HER2 type, but this patient did not have a pCR. pCR pathological complete response, HER2 human epidermal growth factor receptor, BP BluePrint, HR+ hormone receptor-positive, IHC immunohistochemistry, FISH fluorescence in situ hybridization
Fig. 3
Fig. 3
Clinical response rate (cCR and PR) to neoadjuvant endocrine therapy with an aromatase inhibitor in BluePrint Luminal tumors (n = 53). cCR clinical complete response, PR partial response
See this image and copyright information in PMC

References

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