Abstract
A complete oncofertility counselling should be offered to all premenopausal patients before the administration of anticancer treatments. This important discussion is a crucial step for allowing them to take fully informed decisions about the proposed therapy and its potential long-term consequences as well as on their need and interest of accessing the available strategies for ovarian function and/or fertility preservation. In premenopausal women with HER2-positive early breast cancer, limited evidence exists to counsel them about the potential added gonadotoxicity of targeted agents beyond the damage already caused by chemotherapy. In addition, the prognostic role of treatment-induced amenorrhea in this setting was unknown. In our exploratory analysis within the ALTTO (BIG 2-06) trial, we have recently described the rates of treatment-induced amenorrhea after chemotherapy plus trastuzumab and/or lapatinib and the prognostic value of developing this side effect according to the hormone receptor status of their tumours. We observed similar rates of treatment-induced amenorrhea in the four anti-HER2 treatment arms. The lack of an increased rate of treatment-induced amenorrhea in the dual anti-HER2 blockade arm suggests the possible gonadal safety of these agents. In addition, women with HER2-positive/hormone receptor-positive tumours showed significantly better survival outcomes if they developed treatment-induced amenorrhea, while no difference was observed for those with HER2-positive/hormone receptor-negative disease. Future research efforts are needed to address the gonadotoxicity of the new available targeted agents as well as to elucidate which is the best adjuvant endocrine therapy in premenopausal women with HER2-positive/hormone receptor-positive disease.
Highlights
By including 2,862 patients who were premenopausal at randomization, we described the rates of treatment-induced amenorrhea after approximately 9 months following the completion of anthracycline- and/or taxane-based chemotherapy in the four anti-HER2 treatment arms of the trial
The rates of treatment-induced amenorrhea were similar in the four anti-HER2 treatment arms, being 72.6% with trastuzumab alone, 74.0% with lapatinib alone, 72.1% with trastuzumab followed by lapatinib and 74.8% with dual anti-HER2 blockade of trastuzumab plus lapatinib (Figure 1) [4]
The ALTTO trial did not have a treatment arm without anti-HER2 therapies; the answer on the potential added gonadotoxic effect of trastuzumab and/or lapatinib beyond chemotherapy could not be addressed in our study
Summary
The rates of treatment-induced amenorrhea were similar in the four anti-HER2 treatment arms, being 72.6% with trastuzumab alone, 74.0% with lapatinib alone, 72.1% with trastuzumab followed by lapatinib and 74.8% with dual anti-HER2 blockade of trastuzumab plus lapatinib (Figure 1) [4]. Experiencing treatment-induced amenorrhea has been shown to have a positive prognostic impact with improved outcomes in patients with hormone www.oncotarget.com receptor-positive breast cancer by causing a subsequent state of ovarian function suppression [3].
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