High-dose Chemotherapy With Autologous Hematopoietic Stem Cell Transplantation as Adjuvant Treatment for Triple Negative Breast Cancer Patients Without Complete Pathological Response to Neoadjuvant Chemotherapy

Triple-negative breast cancer (TNBC) accounts for approximately 15%-25% of all breast cancer cases. TNBC are usually high-grade tumors, presented among younger women, African American and Hispanic women have a higher risk; generally in advanced stages when diagnosed, with visceral recurrence (liver, lung, brain). Standard treatment is surgery with adjuvant chemotherapy and radiotherapy. As a variation, neoadjuvant chemotherapy is very frequently used for triple-negative breast cancers, however, there is a lack of specific agents for this subset of patients, and, pathologic complete response does correlate with overall survival. At the moment, no optimal chemotherapy exists for TNBC patients who do not achieve a pCR.

According to the German group, in the triple negative subset, 31% of patients with neoadjuvant chemotherapy achieved pathologic complete response (pCR), which correlates with progression free survival (HR 6.02 for those who do not achieve pCR), and an overall survival (HR 12.41 for those who do not achieve pCR).

The usage of high-dose chemotherapy with autologous HSCT, is one of the therapies that have been studied in the patients with localized breast cancer aiming to improve its outcome. Autologous HSCT allows higher chemotherapy doses, which results in higher tumor cells destruction. Since 1980, several phase II studies were performed with high-dose chemotherapy and autologous HSCT, with an apparently initial benefit, thus this strategy was widely used outside controlled clinical trials. Afterward, the randomized studies did not show benefit in overall survival, causing this strategy to be abandoned.

It is important to highlight studies heterogeneity by means of different treatment options in both experimental and control group, besides, advances in autologous HSCT has significantly reduced the complexity, mobility, and mortality related to the chemotherapy treatment.

Two published studies including patients with localized TNBC, showed benefit in the progression free survival in the high-dose chemotherapy group, with a tendency to improved overall survival. One of them was performed by a german group, including patients with at least 9 positive nodes, which were randomized to receive two cycles of conventional dose chemotherapy followed by two cycles of high-dose chemotherapy with autologous HSCT versus four cycles of conventional dose chemotherapy followed by three cycles of dense dose chemotherapy, with granulocyte colony-stimulating factor (G-CSF) administration. Progression free survival was 76 months in the group of high dose chemotherapy versus 40.6 months in the conventional chemotherapy group, with an overall survival of 60 versus 44%, being statistically significant.