Two cases of possible remission in metastatic triple-negative breast cancer

Discussion

Triple-negative breast cancers (TNBCs) are defined as tumors that lack expression of estrogen receptor (ER), progesterone receptor (PR), and HER2, and represent about 12%-17% of breast cancer cases.^1,6 TNBCs tend to be larger in size at diagnosis than are other subtypes, are usually high-grade (poorly differentiated), and are more likely to be invasive ductal carcinomas.^1,7 TNBC and the basal-like breast cancers as a group are associated with an adverse prognosis.^1,7 There is no standard preferred chemotherapy and no biologic therapy available for TNBC.^1,6-7 A sharp decline in survival outcome during the first 3-5 years after diagnosis initial is observed in TNBC, although the distant relapses after this time are less common.¹ Beyond 10 years from diagnosis, the relapses are seen more common among patients with ER-positive cancers than among those with ER-negative subtype cancers. Therefore, although TNBCs are biologically aggressive, many are possibly curable, and this reflects their interesting characteristic heterogeneity.^1,6

Chemotherapy is currently the mainstay of systemic medical treatment. Although patients with TNBC have a worse outcome after chemotherapy than patients with breast cancers of other subtypes, it still improves their outcome to a greater extent than in patients with ER-positive subtypes.^1,6,7 Considering the heterogeneity of TNBC, it is difficult to predict which patients will benefit more from chemotherapy. The same has been observed in previous studies when subgroups of women with TNBC were extremely sensitive to chemotherapy, whereas in others it was of uncertain benefit.¹

Currently, there is no preferred standard form of chemotherapy for TNBC. There are few case reports that demonstrate long-term survival and complete remission in metastatic TNBC. Shakir has reported on a significant clinical response to nab-paclitaxel monotherapy in a patient with triple-negative BRCA1-positive breast cancer, although patient survived a little more than 5 years and died with central nervous system recurrence.⁸ Montero and Gluck have described a patient with metastatic TNBC who was treated with nab-paclitaxel, gemcitabine, and bevacizumab and who also survived for 5 years after diagnosis.⁹ Different retrospective analyses have suggested that the addition of docetaxel or paclitaxel to anthracycline-containing adjuvant regimens may be of greater benefit for the treatment of TNBC than for ER-positive tumors.¹⁰ A meta-analysis of trials comparing the effects of cyclophosphamide, methotrexate, and fluorouracil (CMF, which was used in Case 2) with anthracycline-containing regimens has suggested that the latter therapy regimen is more effective against TNBC,¹¹ although another retrospective analysis of a separate trial suggested the opposite for basal-like breast cancers. ¹² The authors of the latter analysis concluded that anthracycline-containing adjuvant chemotherapy regimens are inferior to adjuvant CMF in women with basal breast cancer.¹²

Miller and colleagues have shown that the addition of bevacizumab (angiogenesis inhibitor) to paclitaxel (used in Case 1) improved progression-free survival (median PFS, 11.8 vs 5.9 months; hazard ratio [HR] for progression, 0.60; P < .001) in women with TNBC as it did in the overall study group (HR, 0.53 and 0.60, respectively), although the overall survival rate was similar in the two groups (median OS, 26.7 vs 25.2 months; HR, 0.88; P = .16).¹³

An interesting clinical target in TNBC is the enzyme poly (adenosine diphosphate– ribose) polymerase (PARP), which is involved in base-excision repair after DNA damage. PARP inhibitors have shown encouraging clinical activity in trials of tumors arising in BRCA mutation carriers and in sporadic TNBC cancers.¹⁴ Similarly, the use of an oral PARP inhibitor, olaparib, resulted in tumor regression in up to 41% of patients carrying BRCA mutations, most of whom had TNBC.¹⁵
 

Conclusion

TNBC and basal-like breast cancers show aggressive clinical behavior, but a subgroup of these cancers may be markedly sensitive to chemotherapy and associated with a good prognosis when treated with conventional chemotherapy regimens. The two cases presented here show that some patients can get a prolonged disease control from chemotherapy, even after progressing on multiple previous chemotherapy regimens and that after, 5 years or so, these rare patients could be in true long-term remission. Novel approaches, for example PARP inhibitors, have shown encouraging clinical activity in trials of tumors arising in BRCA mutation carriers and as well as sporadic TNBC.