Adenoid Cystic Breast Cancer (ACBC)

Overview

Adenoid cystic breast cancer (ACBC) is a rare special-histologic subtype of invasive breast carcinoma, representing approximately 0.1% of all invasive breast cancers. It sits at OncoTree level 3 under BRCA (Invasive Breast Carcinoma). Despite being triple-negative (ER−/PR−/HER2−), ACBC has a favorable prognosis relative to common-type triple-negative breast cancer (TNBC). The defining molecular feature is the t(6;9) MYB-NFIB chromosomal translocation generating a MYB-NFIB fusion transcript, present in the majority of cases. Its genomic landscape strongly resembles adenoid cystic carcinoma of the salivary gland rather than common-type TNBC, with a conspicuously low mutation burden and absence of TP53 and PIK3CA mutations.

Cohorts in the corpus

  • acbc_mskcc_2015 — 12 fresh/frozen and FFPE breast AdCCs from Institut Curie (Paris) and Memorial Sloan Kettering Cancer Center; all triple-negative; histologic grade 1–2; subjected to whole-exome sequencing at median 78× depth PMID:26095796.

Recurrent alterations

  • MYB-NFIB fusion — t(6;9) translocation detected in 10/12 (83%) breast AdCCs by FISH/RT-PCR; most common chimeric transcript is MYB exon 14 — NFIB exon 8c or exon 9 PMID:26095796.
  • MYB — missense mutations in 2/12 (17%) cases; one mutation occurred in the exon 13 splice site of the MYB-NFIB fusion allele PMID:26095796.
  • TLN2 — missense mutations in 2/12 (17%) cases PMID:26095796.
  • BRAF — mutation in 1/12 (8%) in the MSK/Curie cohort; previously reported in 12% (3/25) of an independent cohort PMID:26095796.
  • FBXW7, SF3B1, FGFR2, PRKD1 — non-passenger mutations shared with salivary gland AdCCs PMID:26095796.
  • TP53 and PIK3CA — absent; sharp contrast to common-type TNBC/basal-like breast cancers PMID:26095796.
  • Low overall mutation burden: median 0.27 non-silent mutations/Mb, significantly lower than basal-like (1.41/Mb) and TNBC (1.38/Mb) in TCGA (p<0.001) PMID:26095796.
  • Recurrent copy number losses of 12q12-q14.1 in 5/12 cases (all MYB-NFIB fusion-positive); gains of 17q21-q25.1 in 3/12 cases PMID:26095796.

Subtypes

  • Pure tubular-cribriform (67%), cribriform (17%), solid-cribriform (8%), and solid-trabecular (8%) growth patterns observed in the MSK/Curie cohort; pure and mixed subtypes found to be genetically similar PMID:26095796.
  • MYB-NFIB fusion-negative cases (2/12) may achieve MYB activation through alternative mechanisms PMID:26095796.

Therapeutic landscape

  • BRAF/PIK3CA/TP53-directed therapies used in common-type TNBC are likely to have limited value in ACBC given the absence of these mutations PMID:26095796.
  • Recurrent MYB-NFIB fusion and enrichment for FGF, IGF1, and EMT pathway alterations suggest potential alternative therapeutic angles, though no specific drug-response data were reported PMID:26095796.

Sources

  • PMID:26095796 — Martelotto et al. (2015). Whole-exome sequencing of 12 breast adenoid cystic carcinomas; characterization of MYB-NFIB fusion prevalence, low mutation burden, and genomic distinctiveness from common-type TNBC.

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