Triple-Negative Invasive Breast Carcinoma Clinical Trial
Official title:
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) refers to any breast cancer that does not express estrogen receptor (ER), progesterone receptor (PR) or Her2/neu. Its incidence is approximately 180,000 cases per year. TNBC are known to be more aggressive with poor prognosis specially when no pathologic complete response (pCR) is achieved after neoadjuvant chemotherapy, with a higher risk of recurrence and a poor survival once that recurrence occurs. On the other hand, there is not a specific adjuvant or neoadjuvant treatment for these patients. Since autologous hematopoietic stem cell transplantation (HSCT) allows the usage of higher doses of chemotherapy, which results in higher cellular destruction with a decrease of hematological toxicity, it is proposed that this procedure is able to improve prognosis in TNBC patients with no pathologic complete response after 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.
Our hypothesis is that patients with TNBC with a high risk of recurrence (no pCR) who undergo
high-dose chemotherapy followed by autologous HSCT will have a higher overall survival
compared to those who do not undergo the above mentioned treatment.
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