Past:
Although breast cancer is rare in women under 40 years of age, more and more women are delaying childbearing for personal and professional reasons, increasing the probability that a breast cancer diagnosis may occur prior to completion of childbearing. Indeed, multiple studies have reported significant interest in and concerns regarding fertility among premenopausal women with breast cancer.1 Young women are more likely than their older counterparts to present with locally advanced disease and harbor high-risk molecular subtypes.2 As indications for and use of NAC continue to expand, young women with breast cancer are becoming increasingly likely to receive a recommendation for neoadjuvant chemotherapy (NAC).
NAC provides the ability to deescalate surgical management while also providing prognostic and predictive information; however, chemotherapy is associated with infertility. As a result, the American Society of Clinical Oncology (ASCO) has recommended early referral to reproductive endocrinologists (REI) to discuss fertility preservation. There is a paucity of data regarding how NAC impacts decision making regarding fertility preservation.
Present:
We performed a retrospective review of a prospectively maintained database to identify all women with clinical stage 0-III, unilateral invasive cancer who met with a fertility nurse specialist (FNS) at Memorial Sloan Kettering between 2009 and 2015.3 The FNS would subsequently refer interested patients for REI consultation. In our study, 70% of women chose to consult with an REI. Nulliparity (p < 0.0001) and referral from the Breast Surgery Service (p = 0.002) were associated with pursuing REI consultation. We noted an interesting relationship between timing of chemotherapy and REI referral; while adjuvant chemotherapy was associated with REI referral (p = 0.003), NAC was associated with declining REI referral (p < 0.001), with only 40% of patients accepting REI referral. Multivariate analysis identified referral from the Breast Surgery Service and receipt of NAC as independent predictors of the decision of whether to pursue REI consultation or not. Notably, treatment delays as a result of REI referrals were rare.
Future:
The explanation for the low rate of pursuit of REI referral among patients who receive NAC is likely multifactorial. Recommendation for NAC has been associated with a “scare factor” and a sense of increased urgency to initiate chemotherapy among women with breast cancer. This anxiety, together with difficulty reconciling intentionally elevating estradiol levels for ovarian stimulation while a tumor remains in situ, likely contributes to the low rate of REI consultation among women receiving NAC. This finding is even more important when coupled with the observation that NAC negatively predicts the decision to complete an ovarian stimulation cycle, and highlights the challenges associated with pursuit of fertility preservation in the NAC setting.4
Research refining ovarian stimulation cycles to minimize estradiol levels while maximizing oocyte yields and preventing delays to cancer treatment is ongoing. Although recent studies have reported favorable oncologic and pregnancy outcomes following fertility preservation in women with breast cancer, additional studies in the NAC setting are warranted.5
Footnotes
Publisher's Disclaimer: This Author Accepted Manuscript is a PDF file of an unedited peer-reviewed manuscript that has been accepted for publication but has not been copyedited or corrected. The official version of record that is published in the journal is kept up to date and so may therefore differ from this version.
Disclosures: The authors have no conflict of interests to disclose.
REFERENCES
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