Apocrine carcinoma of the breast: A brief update on the molecular features and targetable biomarkers

Apocrine carcinoma of the breast is a rare, primary breast cancer characterized by the apocrine morphology, estrogen receptor-negative and androgen receptor-positive profile with a frequent overexpression of Her-2/neu protein.

The frequent presence of PIK3CA mutations and androgen overexpression may confer sensitivity to the combination of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) and AR inhibitors.

HER2 amplification and over-expression are seen in ~30% of tumors, while EGFR gene is amplified in a small (6%) percentage of cases despite the common epidermal growth factor receptor (EGFR) protein expression. These two receptors may be targeted with monoclonal antibodies; however the high frequency of PIK3CA mutation may contribute to attenuated responses, and a comprehensive sample profiling is needed to provide optimal personalized therapy.

Biomarkers of classic chemotherapy that are variably expressed in individual cases (and the agents used to target them) include topoisomerase 2 alpha (TOPO2A) [anthracyclines], excision repair cross-complementation group 1 protein (ERCC1) [platinum drugs], ribonucleotide reductase catalytic subunit M1 (RRM1) [gemcitabine], transducin like enhancer of split 3 (TLE3) [taxanes], and thymidylate synthase (TS) [antifolates].

Recently described immune therapies based on immune checkpoint inhibitors have not been described specifically for apocrine carcinomas, which in our limited experience do not express programmed death-ligand 1 (PD-L1).

SAŽETAK NA BOSANSKOM JEZIKU

Apokrini karcinom dojke je rijedak primarni karcinom dojke, karakteriziran apokrinom morfologijom, nedostatkom ekspresije estrogenskog receptore (ER), pozitivnošću na androgenski receptor (AR) uz čestu ekspresiju Her-2/neu proteina. Zbog česte mutacije PIK3CA gena koja je udružena sa ekspresijom AR, pacijentice sa apokrinim karcinomom mogu biti osjetljive na udruženo djelovanje PIK3CA i AR inhibitora.

Aktivacija HER2 je prisutna u otprilike 30% slučajeva dok je amplifikacija EGFR gena prisutna u malome procentu (6%) uprkos čestoj ekspresiji EGFR proteina. Oba gena mogu biti metom ciljanih lijekova (monoklonalnih antitijela). Ipak, zbog česte mutacije PIK3CA gena, djelovanje ovih lijekova može biti atenuirano, zbog čega je neophodno sveobuhvatno molekularno prolifiranje apokrinih carcinoma u svrhu optimiziranja terapije.

Ekspresija biomarkera koji su prediktori odgovora na klasičnu kemoterapiju je dosta varijabilna u apokrinom karcinomu: TOPO2A marker [antraciklini], ERCC1 marker [preparati platine], RRM1 marker [gemcitabin], TLE3 [taksani] i TS [antifolati].
Ekspresija PD-L1 biomarkera se rijetko vidi u apokrinom karcinomu dojke.

This review article was published as:

Vranic S, Feldman R, Gatalica Z. Apocrine carcinoma of the breast: A brief update on the molecular features and targetable biomarkers. Bosn J Basic Med Sci. 2016 Dec 21. doi: 10.17305/bjbms.2016.1811. [Epub ahead of print]