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PIK3CA mutation in ER-negative and HER2-positive breast cancer with apocrine differentiation

Fumi Nozaki1, Yoko Nakanishi2, Yukari Hirotani2

  • 1Division of Oncologic Pathology, Department of Pathology and Microbiology, Nihon University School of Medicine, 30-1, Oyaguchikami-cho, Itabashi-ku, Tokyo, 173- 8610, Japan. fuchinoue.fumi@nihon-u.ac.jp.

Breast Cancer (Tokyo, Japan)
|February 23, 2026
PubMed
Abstract

Insights

PIK3CA mutations are found in apocrine carcinoma, including ER-negative subtypes. These mutations drive cancer cell proliferation, suggesting targeted therapy may benefit patients with apocrine breast cancer.

Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • Targeted therapies for PIK3CA-mutated breast cancer are limited to HR-positive, HER2-negative subtypes.
  • Apocrine carcinoma (apocrine ca.) is typically ER-negative and HER2-positive/negative, excluding it from current PIK3CA-targeted treatments.
  • This study investigates PIK3CA mutations in apocrine ca., especially ER-negative subtypes.

Purpose of the Study:

  • To determine the prevalence of PIK3CA mutations in apocrine carcinoma.
  • To assess the functional significance of PIK3CA mutations in apocrine carcinoma cell proliferation.
  • To explore the potential for PIK3CA-targeted therapies in apocrine ca.

Main Methods:

  • Analyzed hotspot PIK3CA mutations in 20 apocrine ca. and 70 invasive breast carcinoma of no special type (IBC-NST) samples.
  • Utilized PIK3CA knockdown via siRNA to compare proliferation in apocrine ca. cell lines with and without PIK3CA mutations.
  • Compared proliferation rates in MDA-MB-453 (ER-/HER2+/AR+), MFM223 (ER-/HER2-/AR+), and HCC1428 (ER+/HER2-/AR-) cell lines.

Main Results:

  • PIK3CA mutations were found in 15.0% of apocrine ca. and 2.9% of IBC-NST cases.
  • In ER-negative, HER2-positive subtypes, 25% of apocrine ca. had PIK3CA mutations, versus 0% in IBC-NST.
  • PIK3CA knockdown significantly reduced proliferation in MDA-MB-453 and MFM223 apocrine ca. cell lines.

Conclusions:

  • PIK3CA mutations are present in ER-negative and HER2-positive apocrine ca.
  • These mutations drive PIK3CA-dependent proliferation in vitro.
  • Apocrine ca. patients may benefit from PIK3CA mutation testing and targeted therapy.
Keywords:
Breast cancerCarcinoma with apocrine differentiationPI3KPIK3CA

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