National Breast Cancer Coalition

Triple Negative Breast Cancer

We know that not all breast cancers are the same. Though we have known for some time that some breast cancers express excess estrogen receptors, we now know that there are several types of breast cancer based on the biology of the tumors. These subtypes respond to different treatments and have different prognoses. Though more will likely be identified in the future, breast tumors are currently classified using five immunohistochemical (IHC) tumor markers: estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), HER-1, and cytokeratin 5/6 (CK 5/6) (Carey, 2006). Based on expression of these markers, breast tumors are classified into the following subtypes: luminal A (ER+ and/or PR+, HER-2-); luminal B (ER+ and/or PR+, HER-2+); HER-2+ (and ER-, PR-); basal-like (ER-, PR-, HER-2-, HER-1+, and/or CK 5/6+); and normal (negative for all five markers) (O’Brien, 2010).

Approximately 70% of "triple negative" breast cancers (TNBC) are basal-like, therefore triple negative is often used as a surrogate for basal-like subtype (Bertucci, 2008; Bidard, 2007). These different subtypes of breast cancer behave differently, are associated with different populations of women and different risk factors, and may have different causes. However, current annual incidence and mortality statistics are reported for breast cancer overall and not by subtype.

Recent research into treatment for triple negative breast cancer.

After promising Phase II results suggesting that BSI-201(iniparib), a poly (ADP-ribose) polymerase (PARP) inhibitor extended survival by an average of almost five months over chemotherapy alone in triple negative cancers (O'Shaughnessy, NEJM, 2011), many had hope that PARP inhibitors would be the major advance in treatment in 2011. Unfortunately, early that year, BiPar Sciences announced disappointing results from their randomized Phase III trial evaluating the PARP inhibitor, BSI-201 (iniparib), in patients with metastatic triple negative breast cancer (O’Shaughnessy, JCO, 2011). The Phase III results found no improvement in overall or progression-free survival in first line treatment.

References

Bertucci F, Finetti P, Cervera N, et al. How basal are triple-negative breast cancers? International Journal of Cancer. 2008;123(1):236-240.

Bidard F-C, Conforti R, Boulet T, Michiels S, Delaloge S, Andre F. Does triple-negative phenotype accurately identify basal-like tumour?  An immunohistochemical analysis based on 143 ‘triple-negative’ breast cancers. Annals of Oncology. July 1, 2007;18(7):1285-1286.

Carey LA, Perou CM, Livasy CA, et al. Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA. Jun 7 2006;295(21):2492-2502.

O’Brien KM, Cole SR, Tse CK, et al. Intrinsic breast tumor subtypes, race, and long-term survival in the Carolina Breast Cancer Study. Clin Cancer Res. Dec 15 2010;16(24):6100-6110.

O'Shaughnessy J, Osborne C, Pippen JE, Yoffe M, Patt D, Rocha C, Koo IC, Sherman BM, Bradley C: Iniparib plus chemotherapy in metastatic triple-negative breast cancer. N Engl J Med 2011, 364(3):205-214.

O’Shaughnessy J, Schwartzberg LS, Danso MA, Rugo HS, Miller K et al.: A randomized phase III study of iniparib (BSI-201) in combination with gemcitabine/carboplatin (G/C) in metastatic triple negative breast cancer. J Clin Oncol 2011, 29(supplement, abstract 1007).