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Certain adjuvant therapies reduce risk for contralateral breast cancer
Patients with breast cancer who received adjuvant endocrine therapy, chemotherapy, or a combination of trastuzumab and chemotherapy demonstrated a reduced risk for contralateral breast cancer, according to results of a retrospective study published in Journal of the National Cancer Institute.
“Breast cancer survival has increased considerably, largely as a result of increasing use of (neo)adjuvant therapies,” Iris Kramer, PhD student in the division of molecular pathology and division of psychosocial research and epidemiology at the Netherlands Cancer Institute, and colleagues wrote. “As a consequence, a greater number of women are at risk [for] developing a second primary tumor in the contralateral breast. “Patients [with contralateral breast cancer] may have a worse prognosis compared to patients with unilateral [breast cancer]. An explanation for this worse prognosis, besides having been diagnosed with yet another cancer, may be found in the impact of adjuvant systemic therapy on [contralateral breast cancer] tumor biology, or due to misclassification of metastatic disease as a [contralateral breast cancer].”
Kramer and colleagues sought to determine whether specific adjuvant therapies influenced the risk for contralateral breast cancer, overall and by hormone receptor subtype. They used the Netherlands Cancer Registry through linkage with the Dutch Pathology Registry to identify 83,144 women (median age at diagnosis, 58.5 years) diagnosed with first invasive breast cancer between 2003 and 2010 who underwent surgery.
Median follow-up was 7.7 years (range, 0.3-13.1).
Among all women in the cohort, 2,816 developed invasive contralateral breast cancer a median 4.6 years (range, 0.3-12.7) after first breast cancer.
Results showed cumulative contralateral breast cancer incidence of 1.9% (95% CI, 1.8-2) at 5 years and 3.8% (95% CI, 3.7-4) at 10 years.
Adjuvant chemotherapy (HR = 0.7; 95% CI, 0.62-0.8), endocrine therapy (HR = 0.46; 95% CI, 0.41-0.52), and trastuzumab (Herceptin, Genentech) in combination with chemotherapy (HR = 0.57; 95% CI, 0.45-0.73) strongly decreased risk for contralateral breast cancer.
Taxane-containing chemotherapy (HR = 0.48; 95% CI, 0.36-0.62) and aromatase inhibitors (HR = 0.32; 95% CI, 0.23-0.44) were specifically associated with large reductions in contralateral breast cancer risk.
Women who received endocrine therapy had a statistically significant decreased risk for ER-positive (HR = 0.41; 95% CI, 0.36-0.47) but not ER-negative (HR = 1.32; 95% CI, 0.9-1.93) contralateral breast cancer compared with women who received no endocrine therapy.
Women who received chemotherapy for ER-negative first breast cancer had a higher risk for ER-negative contralateral breast cancer after at least 5 years of follow-up (HR = 2.84; 95% CI, 1.62-4.99) compared with women who did not receive chemotherapy.
Researchers observed no association between radiotherapy and risk for contralateral breast cancer (HR = 0.94; 95% CI, 0.86-1.02).
Women diagnosed with stage 3 first breast cancer appeared at significantly higher risk for contralateral breast cancer than women diagnosed with stage 1 or stage 2 first breast cancer (HR = 1.48; 95% CI, 1.3-1.69). This did not apply if distant metastases and death were considered as competing risks.
Women aged 45 to 54 years (HR = 0.88; 95% CI, 0.8-0.98) and 85 years and older (HR = 0.55; 95% CI, 0.37-0.81) appeared at a lower risk for contralateral breast cancer than women aged 55 to 64 years.
A lack of data on contralateral prophylactic mastectomy as well as differing patient and tumor characteristics among women who did and did not receive adjuvant therapy served as limitations to this study.
“According to this study, there is no clear indication to change current guidelines on adjuvant systemic therapy,” Kramer and colleagues wrote. “Further research disentangling true primary [contralateral breast cancer] from metastases may be useful in further personalization of [contralateral breast cancer] prevention and treatment choices.”
In an accompanying editorial, Kevin J. Cheung, MD, assistant member of the public health services division at Fred Hutchinson Cancer Research Center, and Nancy E. Davidson, MD, senior vice president and director and full member of the clinical research division at Fred Hutchinson Cancer Research Center, wrote that further studies should test these risks in different populations because the majority of women in this study were white.
“In the modern era, risk estimation will be increasingly individualized,” Cheung and Davidson wrote. “Future studies should determine whether these results hold true for ethnically diverse as well as high-risk populations, including patients with strong family history of bilateral breast cancer and patients that are BRCA1 [or] BRCA2 mutation carriers.”– by John DeRosier
Disclosures: This study was funded by the Dutch Cancer Society. The study authors and editorial authors report no relevant financial disclosures.