Background: The potential gonadotoxicity of anti-HER2 agents remains largely unknown, and limited, conflicting evidence exists for taxanes. Antimüllerian hormone (AMH) is an established biomarker of ovarian reserve that may aid in quantifying anticancer treatment–induced gonadotoxicity. Patients and Methods: The present biomarker analysis of the randomized phase III neoadjuvant NeoALTTO trial included premenopausal women aged ≤45 years at diagnosis of HER2-positive early breast cancer with available frozen serum samples at baseline (ie, before anticancer treatments), at week 2 (ie, the “biological window” of anti-HER2 therapy alone), and/or at the time of surgery (ie, after completing paclitaxel + anti-HER2 therapy, before starting adjuvant chemotherapy). Results: The present analysis included 130 patients with a median age of 38 years (interquartile ratio [IQR], age 33–42 years). AMH values at the 3 time points differed significantly (P<.001). At baseline, median AMH levels were 1.29 ng/mL (IQR, 0.56–2.62 ng/mL). At week 2, a small but significant reduction in AMH levels was observed (median, 1.10 ng/mL; IQR, 0.45–2.09 ng/mL; P<.001). At surgery, a larger significant decline in AMH levels was observed (median, 0.01 ng/mL; IQR, 0.01–0.03 ng/mL; P<.001). Although the type of anti-HER2 treatment (trastuzumab and/or lapatinib) did not seem to impact the results, age and pretreatment ovarian reserve had a major influence on treatment-induced gonadotoxicity risk. Conclusions: This NeoALTTO biomarker analysis showed that anti-HER2 therapies alone had limited gonadotoxicity but that the addition of weekly paclitaxel resulted in marked AMH decline with possible negative implications for subsequent ovarian function and fertility.
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Impact of Anti-HER2 Therapy Alone and With Weekly Paclitaxel on the Ovarian Reserve of Young Women With HER2-Positive Breast Cancer
Matteo Lambertini, Marcello Ceppi, Richard A. Anderson, David A. Cameron, Marco Bruzzone, Maria Alice Franzoi, Claudia Massarotti, Sarra El-Abed, Yingbo Wang, Christophe Lecocq, Paolo Nuciforo, Rebecca Rolyance, Lajos Pusztai, Joohyuk Sohn, Maria Maddalena Latocca, Luca Arecco, Barbara Pistilli, Kathryn J. Ruddy, Alberto Ballestrero, Lucia Del Mastro, Fedro A. Peccatori, Ann H. Partridge, Cristina Saura, Michael Untch, Martine Piccart, Serena Di Cosimo, Evandro de Azambuja, and Isabelle Demeestere
Uptake of Recommendations for Posttreatment Cancer-Related Fatigue Among Breast Cancer Survivors
Antonio Di Meglio, Cecile Charles, Elise Martin, Julie Havas, Arnauld Gbenou, Jean-Daniel Flaysakier, Anne-Laure Martin, Sibille Everhard, Enora Laas, Nicolas Chopin, Laurence Vanlemmens, Christelle Jouannaud, Christelle Levy, Olivier Rigal, Marion Fournier, Patrick Soulie, Florian Scotte, Barbara Pistilli, Agnes Dumas, Gwenn Menvielle, Fabrice André, Stefan Michiels, Sarah Dauchy, and Ines Vaz-Luis
Background: Physical activity (PA) and psychosocial interventions are recommended management strategies for cancer-related fatigue (CRF). Randomized trials support the use of mind–body techniques, whereas no data show benefit for homeopathy or naturopathy. Methods: We used data from CANTO (ClinicalTrials.gov identifier: NCT01993498), a multicenter, prospective study of stage I–III breast cancer (BC). CRF, evaluated after primary treatment completion using the EORTC QLQ-C30 (global CRF) and QLQ-FA12 (physical, emotional, and cognitive dimensions), served as the independent variable (severe [score of ≥40/100] vs nonsevere). Outcomes of interest were adherence to PA recommendations (≥10 metabolic equivalent of task [MET] h/week [GPAQ-16]) and participation in consultations with a psychologist, psychiatrist, acupuncturist, or other complementary and alternative medicine (CAM) practitioner (homeopath and/or naturopath) after CRF assessment. Multivariable logistic regression examined associations between CRF and outcomes, adjusting for sociodemographic, psychologic, tumor, and treatment characteristics. Results: Among 7,902 women diagnosed from 2012 through 2017, 36.4% reported severe global CRF, and 35.8%, 22.6%, and 14.1% reported severe physical, emotional, and cognitive CRF, respectively. Patients reporting severe global CRF were less likely to adhere to PA recommendations (60.4% vs 66.7%; adjusted odds ratio [aOR], 0.82; 95% CI, 0.71–0.94; P=.004), and slightly more likely to see a psychologist (13.8% vs 7.5%; aOR, 1.29; 95% CI, 1.05–1.58; P=.014), psychiatrist (10.4% vs 5.0%; aOR, 1.39; 95% CI, 1.10–1.76; P=.0064), acupuncturist (9.8% vs 6.5%; aOR, 1.46; 95% CI, 1.17–1.82; P=.0008), or CAM practitioner (12.5% vs 8.2%; aOR, 1.49; 95% CI, 1.23–1.82; P<.0001). There were differences in recommendation uptake by CRF dimension, including that severe physical CRF was associated with lower adherence to PA (aOR, 0.74; 95% CI, 0.63–0.86; P=.0001) and severe emotional CRF was associated with higher likelihood of psychologic consultations (aOR, 1.37; 95% CI, 1.06–1.79; P=.017). Conclusions: Uptake of recommendations to improve CRF, including adequate PA and use of psychosocial services, seemed suboptimal among patients with early-stage BC, whereas there was a nonnegligible interest in homeopathy and naturopathy. Findings of this large study indicate the need to implement recommendations for managing CRF in clinical practice.
Uptake of Recommendations for Posttreatment Cancer-Related Fatigue Among Breast Cancer Survivors
Antonio Di Meglio, Cecile Charles, Elise Martin, Julie Havas, Arnauld Gbenou, Jean-Daniel Flaysakier, Anne-Laure Martin, Sibille Everhard, Enora Laas, Nicolas Chopin, Laurence Vanlemmens, Christelle Jouannaud, Christelle Levy, Olivier Rigal, Marion Fournier, Patrick Soulie, Florian Scotte, Barbara Pistilli, Agnes Dumas, Gwenn Menvielle, Fabrice André, Stefan Michiels, Sarah Dauchy, and Ines Vaz-Luis
Background: Physical activity (PA) and psychosocial interventions are recommended management strategies for cancer-related fatigue (CRF). Randomized trials support the use of mind–body techniques, whereas no data show benefit for homeopathy or naturopathy. Methods: We used data from CANTO (ClinicalTrials.gov identifier: NCT01993498), a multicenter, prospective study of stage I–III breast cancer (BC). CRF, evaluated after primary treatment completion using the EORTC QLQ-C30 (global CRF) and QLQ-FA12 (physical, emotional, and cognitive dimensions), served as the independent variable (severe [score of ≥40/100] vs nonsevere). Outcomes of interest were adherence to PA recommendations (≥10 metabolic equivalent of task [MET] h/week [GPAQ-16]) and participation in consultations with a psychologist, psychiatrist, acupuncturist, or other complementary and alternative medicine (CAM) practitioner (homeopath and/or naturopath) after CRF assessment. Multivariable logistic regression examined associations between CRF and outcomes, adjusting for sociodemographic, psychologic, tumor, and treatment characteristics. Results: Among 7,902 women diagnosed from 2012 through 2017, 36.4% reported severe global CRF, and 35.8%, 22.6%, and 14.1% reported severe physical, emotional, and cognitive CRF, respectively. Patients reporting severe global CRF were less likely to adhere to PA recommendations (60.4% vs 66.7%; adjusted odds ratio [aOR], 0.82; 95% CI, 0.71–0.94; P=.004), and slightly more likely to see a psychologist (13.8% vs 7.5%; aOR, 1.29; 95% CI, 1.05–1.58; P=.014), psychiatrist (10.4% vs 5.0%; aOR, 1.39; 95% CI, 1.10–1.76; P=.0064), acupuncturist (9.8% vs 6.5%; aOR, 1.46; 95% CI, 1.17–1.82; P=.0008), or CAM practitioner (12.5% vs 8.2%; aOR, 1.49; 95% CI, 1.23–1.82; P<.0001). There were differences in recommendation uptake by CRF dimension, including that severe physical CRF was associated with lower adherence to PA (aOR, 0.74; 95% CI, 0.63–0.86; P=.0001) and severe emotional CRF was associated with higher likelihood of psychologic consultations (aOR, 1.37; 95% CI, 1.06–1.79; P=.017). Conclusions: Uptake of recommendations to improve CRF, including adequate PA and use of psychosocial services, seemed suboptimal among patients with early-stage BC, whereas there was a nonnegligible interest in homeopathy and naturopathy. Findings of this large study indicate the need to implement recommendations for managing CRF in clinical practice.