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Evolving Paradigms in Triple-Negative Breast Cancer: Treatment

Published Online: Feb 27,2017

Treatment of TNBC

 

Surgical treatment of TNBC

 

With a lack of ERs, PRs, and HER2 as potential treatment targets, TNBC cannot be treated with conventional breast cancer hormonal-based or trastuzumab-based treatments. Patients are typically treated with a combination of surgery, chemotherapy, and radiation.1 In fact, an emphasis is placed on local and regional treatment, such as radiation and surgery, for early-stage disease.

 

With the exception of advanced and inoperable metastatic breast cancer, breast-conserving surgery (BCS), simple mastectomy, or radical mastectomy have remained initial treatments for breast cancer. However, 75% to 85% women with the BRCA1 mutation have the TNBC subtype that influences the type of surgery selected. Although mastectomy to reduce risk of recurrence is preferred over BCS, it is not clear if surgical recommendations should be altered for patients with TNBC. For example, a retrospective study of patients with TNBC treated with mastectomy compared with BCS assessed overall survival (OS) and DFS. The investigators concluded that BCS in TNBC should be considered in selected patients.15

 

Research also indicates that BCS is an appropriate option in TNBC because recurrence after BCS is no higher than that for other types of breast cancer. Furthermore, when choosing a surgical approach, the preferences of the patient, as well as clinical and pathologic variables, should be considered.

 

Radiation Therapy in TNBC

Radiation therapy (RT) after BCS has shown to be beneficial in the long term for patients with breast cancer. Therefore, RT is indicated in TNBC after mastectomy or after BCS despite some controversy.1 For example, one study suggested possible radio resistance due to ER-negative status in TNBC. This is thought to be related to more time available for DNA damage repair from radiation in ER-negative cells.15

 

Conversely, as a result of the aggressive and rapid-growing nature of TNBC, RT after BCS may not be as effective as mastectomy. Because many patients with TNBC have a mutated BRCA1 gene, which lacks double-stranded DNA repair, theoretically they should be very radiosensitive. Some researchers suggest that RT of the surrounding breast tissue after BCS could eliminate remaining mutated BRCA1 foci and lessen the risk of local or regional recurrence.1

 

Therefore, in light of the conflicting data, either BCS or modified radical mastectomy is considered an acceptable choice in early stages of TNBC. Research has indicated an improvement in 5-year relapse-free survival (RFS) and OS with the addition of RT to modified radical mastectomy. Treatment may also include neo-adjuvant chemotherapy with or without RT. Retrospective data indicate that patients treated with chemotherapy and reclassified as stage I or II may not benefit from RT compared with patients with persistent nodal disease. However, with a lack of controlled, prospective studies, the standard of care continues to involve RT after neoadjuvant chemotherapy.16

 

Chemotherapy in TNBC

Although TNBC is considered to be quite responsive to chemotherapy, the combination of aggressive behavior and metastatic course, with a short disease-free period, can make the prognosis of TNBC poor. Chemotherapeutic targets include cell proliferation with anthracyclines, p53 with taxanes, and DNA repair complexes with platinum and taxane regimens.1

 



Platinum-based regimens

 

 

Platinum therapies, such as cisplatin, lead to double-strand breaks and cross linking of double-stranded DNA. In cases of the BRCA1 mutation, platinum therapy leads to cell death by inability to repair the damaged DNA. With research indicating that TNBC may be more sensitive to platinum-based regimens, there is a new push for understanding how to incorporate these regimens into breast cancer treatments. For example, 21% of patients with TNBC treated with neoadjuvant cisplatin in a phase II study had complete response (CR) with 50% showing a good response.17

 

Ezzat and colleagues combined cisplatin with paclitaxel and found a 63% partial response rate and a 28% CR rate in patients with HER2-negative, ER-negative breast cancer. Likewise, patients with TNBC treated with a combination of neoadjuvant cisplatin, paclitaxel, and epirubicin for 8 weeks had a 65% pathologic CR.1

 


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Evolving Paradigms in Triple-Negative Breast Cancer: Treatment
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