Young Women with Breast Cancer: Fertility Preservation Options and Management of Pregnancy-Associated Breast Cancer

BACKGROUND: Breast cancer is the most common malignancy diagnosed in women of childbearing age. A breast cancer diagnosis in this young patient population can be uniquely complex to navigate when considering the potential impact of fertility loss associated with specific gonadotoxic therapies. Another unique challenge for young breast cancer patients is pregnancy-associated breast cancer (PABC), which occurs in approximately 1 of every 3000 pregnancies. Pregnancy adds a layer of complexity to breast cancer treatment planning as many therapies can affect the developing fetus. These two clinical challenges require nuanced multidisciplinary approaches to facilitate optimal treatment outcomes. We sought to review and summarize the management strategy options for both fertility preservation and PABC. METHODS: A guideline and literature review was performed for fertility preservation, young patients with breast cancer, and pregnancy-associated breast cancer. RESULTS: Fertility preservation options, both established and experimental, are detailed. Suggested clinical practice guidelines for PABC are also presented, which delineate breast cancer treatment recommendations based on pregnancy trimester. CONCLUSION: A multidisciplinary approach to patient care, including oncologists and early referral to reproductive specialists, can provide young breast cancer patients with options for fertility preservation. Under the guidance of a multidisciplinary treatment team, PABC can also be diagnosed and treated to permit the best possible outcomes for the mother and the developing fetus

Evaluating Serum Thymidine Kinase 1 in Hormone Receptor Positive Metastatic Breast Cancer Patients Receiving First Line Endocrine Therapy in the SWOG S0226 Trial

PurposeSerum thymidine kinase 1 (sTK1) activity is associated with poor prognosis in metastatic breast cancer (MBC). We assessed the prognostic effect of sTK1 in patients with hormone receptor-positive MBC treated on a prospective randomized trial of anastrozole (A) versus A plus fulvestrant (A + F).Patients and methodssTK1 was assessed in 1,726 serums [baseline (BL), cycles 2, 3, 4, and 7] using the DiviTum assay. A prespecified cutoff of ≥200 Du/L was considered high. Progression-free survival (PFS) and overall survival (OS) were analyzed by Kaplan-Meier, log-rank tests, and Cox regression.ResultsBL sTK1 was elevated in 171 (40%) of 432 patients. Patients with high versus low BL sTK1 had significantly worse PFS [median 11.2 vs. 17.3 months, HR = 1.76; 95% confidence interval (CI; 1.43-2.16); P < 0.0001] and OS [median 30 vs. 58 months, HR = 2.38; 95% CI (1.91-2.98); P < 0.0001]. OS was significantly better for patients with high sTK1 who did not have prior adjuvant tamoxifen and who received A + F versus A alone [median 46 vs. 21 months, HR = 0.58; 95% CI (0.38-0.87); P = 0.0087]. Patients with low sTK1 had no difference in outcomes by therapy (P = 0.44). At serial timepoints, high versus low sTK1 had significantly worse subsequent PFS and OS [at cycle 2: PFS HR = 1.70, 95% CI (1.34-2.17); P < 0.0001, OS HR = 2.51, 95% CI (1.93-3.26); P < 0.0001].ConclusionsHigh sTK1 at BL and subsequent timepoints is associated with worse prognosis in patients with MBC starting first-line endocrine therapy (ET). Patients with low sTK1 at BL have comparable outcomes on single-agent or combination ET

Thymidine kinase activity levels in serum can identify HR+ metastatic breast cancer patients with a low risk of early progression (SWOG S0226)

BackgroundSome patients with metastatic breast cancer (MBC) stay on endocrine therapy (ET) for years and others progress quickly. Serum thymidine kinase activity (TKa), an indicator of cell-proliferation, is a potential biomarker for monitoring ET and predicting MBC outcome. We have previously reported TKa as being prognostic in MBC in SWOG S0226. Here, new data on progression within 30/60 days post sampling, with a new, FDA approved version of DiviTum®TKa highlighting differences vs. a Research Use Only version is reported.Methods1,546 serum samples from 454 patients were assessed, collected at baseline and at 4 subsequent timepoints during treatment. A new predefined cut-off tested the ability to predict disease progression. A new measuring unit, DuA (DiviTum® unit of Activity) is adopted.ResultsA DiviTum®TKa score <250 DuA provides a much lower risk of progression within 30/60 days after blood draw, the negative predictive value (NPV) was 96.7% and 93.5%, respectively. Patients <250 DuA experienced significantly longer progression-free survival and overall survival, demonstrated at baseline and for all time intervals.ConclusionsDiviTum®TKa provides clinically meaningful information for patients with HR+ MBC. Low TKa levels provide such a high NPV for rapid progression that such patients might forego additional therapy added to single agent ET.Trial registration: NCT00075764