Breast cancer (BC) is a serious threat to women’s health of malignant tumors. According to the latest national cancer statistics released by the National Cancer Center, breast cancer is still the highest incidence of malignant tumors in women. In recent years, with the use of new adjuvant therapy, the survival rate of breast cancer has increased significantly. As a result, the risk of contralateral breast cancer (CBC) is also increasing among breast cancer survivors, with studies showing a 10-year risk of CBC of 4% ~7%. Moreover, the prognosis of CBC patients may be worse than that of unilateral BC patients.
There is growing evidence that patients receiving adjuvant endocrine therapy or adjuvant chemotherapy have a lower risk of developing CBC. The early breast cancer trial collaboration group (EBCTCG) showed that after 10 years of follow-up, tamoxifen for 5 years reduced the risk of CBC by 38%, and adjuvant chemotherapy reduced the risk by 20%.
At present, the relationship between adjuvant therapy and CBC hormone receptor subtypes is not clear. Some studies have shown that ER (estrogen receptor negative) patients have an increased risk of CBC after endocrine therapy compared with those who do not receive endocrine therapy. But these are only small-scale studies that need to be further verified. In addition, trastuzumab was approved for the treatment of early BC in 2005, but its effect on CBC is still unknown.
Therefore, in order to study the effects of different treatment regimens, including adjuvant endocrine therapy, adjuvant chemotherapy, and trastuzumab therapy, on the prevention of CBC, the researchers conducted a large-scale study. The results were published in the Journal of the National Cancer Institute. It has very important guiding significance for clinical drug use.
The study included 83144 women diagnosed with invasive breast cancer between 2003 and 2010, all of whom underwent surgical treatment with a median follow-up of 7.7 years.
It was found that:
A total of 2816 patients had CBC, with a median occurrence time of 4.6 years.
The 5-year cumulative risk of CBC was 1.9% (95% CI=1.8-2.0%).
The cumulative risk of contralateral breast cancer in 10 years was 3.8% (95% CI=3.7-4.0%).
The cumulative risk of CBC increased by 0.4% per annum.
The researchers also found that patients who were first diagnosed with stage III breast cancer had a nearly half higher risk of developing CBC than patients with stage I-II.
Through the analysis of multivariate CPH model, it is found that:
Adjuvant chemotherapy could reduce the risk of CBC to 70% (HR=0.70; 95%CI=0.62-0.80).
Endocrine therapy could be reduced to 46% (HR=0.46; 95%CI=0.41-0.52);
Endocrine therapy combined with chemotherapy could be reduced to 35% (HR=0.35; 95%CI=0.31-0.39).
Chemotherapy combined with trastuzumab reduced the risk to 57% (HR=0.57; 95%CI=0.45-0.73).
Trastuzumab combined with endocrine therapy and chemotherapy could minimize the risk of CBC by 24% (HR=0.24; 95%CI=0.17-0.33).
(As shown in the table below).
In chemotherapeutic drugs, chemotherapeutic drugs containing taxanes (paclitaxel, docetaxel, etc.) can reduce the risk of contralateral breast cancer (HR=0.48; 95%CI=0.44-0.53) by 52%; in endocrine therapy drugs, Aromatase inhibitors (letrozole and anastrozole) reduced the risk of contralateral breast cancer by 68% (HR=0.32; 95%CI=0.23-0.44). Not all breast cancer patients are treated with adjuvant therapy after surgery, which can reduce the risk of CBC.
For ER-negative breast cancer, endocrine therapy after surgery increased the risk of contralateral breast cancer by 32% (HR=1.32; 95%CI=0.86-2.04). If chemotherapy is performed after surgery, the risk of contralateral breast cancer increases by 18.4% (HR=2.84; 95%CI=1.62-4.99).
Which adjuvant therapy regimen can minimize the risk of contralateral breast cancer in patients with breast cancer after the operation? The study gave the answer: endocrine therapy, chemotherapy, and trastuzumab combined chemotherapy were observed to reduce the incidence of contralateral breast cancer. However, the impact of each adjuvant treatment regimen is different. In general, chemotherapy regimens containing taxanes and endocrine therapy with aromatase inhibitors can maximize the risk of contralateral breast cancer.
1. Kramer, I., Schaapveld, M., Oldenburg, H. S., Sonke, G. S., McCool, D., van Leeuwen, F. E., … & Schmidt, M. K. (2019). The influence of adjuvant systemic regimens on contralateral breast cancer risk and receptor subtype. JNCI: Journal of the National Cancer Institute.
2. Al-Hajj, M., Wicha, M. S., Benito-Hernandez, A., Morrison, S. J., & Clarke, M. F. (2003). Prospective identification of tumorigenic breast cancer cells. Proceedings of the National Academy of Sciences, 100(7), 3983-3988.