H. Irene Su

Body size affects measures of ovarian reserve in late reproductive age women.

Objective: To examine the association between obesity and serum and ultrasound measures of ovarian reserve in late reproductive age women. Design: Cross-sectional study of 36 healthy women, ages 40 to 52 years. Women were recruited in a 1:1 ratio of normal weight (body mass index <25) to obese women (body mass index ≥30). Early follicular phase blood draw, anthropometric measurements, and a transvaginal ultrasonography were performed. Outcome measures were serum antimullerian hormone, inhibin B, estradiol, follicle-stimulating hormone, ultrasound ovarian volume, and antral follicle count. Results: Mean antral follicle count was 7.6 for normal weight and 6.3 for obese women (P = 0.35). Proportions of normal weight (17%) versus obese women (22%) with antral follicle count less than 4 were similar. Ovarian volumes did not differ by body size. In adjusted models, antimullerian hormone levels in obese women were 77% lower on average than those in normal weight women (P = 0.02). Inhibin B levels were 24% lower in obese women compared with normal weight women (P = 0.08). Follicle-stimulating hormone and estradiol were not associated with body mass index. Conclusions: Although antral follicle count did not differ by body size, antimullerian hormone was lower in obese compared with normal weight late reproductive age women. These data suggest that lower antimullerian hormone levels in obese late reproductive age women result from physiologic processes other than decreased ovarian reserve.

Antimullerian hormone and inhibin B are hormone measures of ovarian function in late reproductive-aged breast cancer survivors.

In late reproductive‐aged breast cancer survivors, there is a need for real‐time biomarkers of postchemotherapy ovarian function. The objective was to determine whether antimullerian hormone (AMH) and inhibin B are such biomarkers. The authors tested whether AMH and inhibin B were impacted by breast cancer treatment by comparing cancer survivors to age‐matched control women and determined the association between these hormones and postchemotherapy menstrual pattern.

Association of functional polymorphisms in CYP19A1 with aromatase inhibitor associated arthralgia in breast cancer survivors

IntroductionAromatase inhibitor-associated arthralgia (AIAA) is a common and often debilitating symptom in breast cancer survivors. Since joint symptoms have been related to estrogen deprivation through the menopausal transition, we hypothesized that genetic polymorphisms in CYP19A1, the final enzyme in estrogen synthesis, may be associated with the occurrence of AIAA.MethodsWe performed a cross-sectional study of postmenopausal women with stage 0 to III breast cancer receiving adjuvant aromatase inhibitor (AI) therapy. Patient-reported AIAA was the primary outcome. DNA was genotyped for candidate CYP19A1 polymorphisms. Serum estrogen levels were evaluated by radioimmunoassay. Multivariate analyses were performed to examine associations between AIAA and genetic variants controlling for possible confounders.ResultsAmong 390 Caucasian participants, 50.8% reported AIAA. Women carrying at least one 8-repeat allele had lower odds of AIAA (adjusted odds ratio (AOR) 0.41, 95% confidence interval (CI) 0.21 to 0.79, P = 0.008) after adjusting for demographic and clinical covariates. Estradiol and estrone were detectable in 47% and 86% of subjects on AIs, respectively. Although these post-AI levels were associated with multiple genotypes, they were not associated with AIAA. In multivariate analyses, women with more recent transition into menopause (less than five years) were significantly more likely to report AIAA than those greater than ten years post-menopause (AOR 3.31, 95% CI 1.72 to 6.39, P < 0.001).ConclusionsFunctional polymorphism in CYP19A1 and time since menopause are associated with patient-reported AIAA, supporting the hypothesis that the host hormonal environment contributes to the pathophysiology of AAIA. Prospective investigation is needed to further delineate relationships between host genetics, changing estrogen levels and AIAA.

Cyclophosphamide-metabolizing enzyme polymorphisms and survival outcomes after adjuvant chemotherapy for node-positive breast cancer: a retrospective cohort study.

IntroductionCyclophosphamide-based adjuvant chemotherapy is a mainstay of treatment for women with node-positive breast cancer, but is not universally effective in preventing recurrence. Pharmacogenetic variability in drug metabolism is one possible mechanism of treatment failure. We hypothesize that functional single nucleotide polymorphisms (SNPs) in drug metabolizing enzymes (DMEs) that activate (CYPs) or metabolize (GSTs) cyclophosphamide account for some of the observed variability in disease outcomes.MethodsWe performed a retrospective cohort study of 350 women enrolled in a multicenter, randomized, adjuvant breast cancer chemotherapy trial (ECOG-2190/INT-0121). Subjects in this trial received standard-dose cyclophosphamide, doxorubicin and fluorouracil (CAF), followed by either observation or high-dose cyclophosphamide and thiotepa with stem cell rescue. We used bone marrow stem cell-derived genomic DNA from archival specimens to genotype CYP2B6, CYP2C9, CYP2D6, CYP3A4, CYP3A5, GSTM1, GSTT1, and GSTP1. Cox regression models were computed to determine associations between genotypes (individually or in combination) and disease-free survival (DFS) or overall survival (OS), adjusting for confounding clinical variables.ResultsIn the full multivariable analysis, women with at least one CYP3A4 *1B variant allele had significantly worse DFS than those who were wild-type *1A/*1A (multivariate hazard ratio 2.79; 95% CI 1.52, 5.14). CYP2D6 genotype did not impact this association among patients with estrogen receptor (ER) -positive tumors scheduled to receive tamoxifen.ConclusionsThese data support the hypothesis that genetic variability in cyclophosphamide metabolism independently impacts outcome from adjuvant chemotherapy for breast cancer.

To preserve or not to preserve: how difficult is the decision about fertility preservation?

The decision to pursue fertility preservation (FP) after a cancer diagnosis is complex. We examined the prevalence of high decisional conflict and specific factors that influence this decision using the Decisional Conflict Scale (DCS).

Association of cyclophosphamide drug–metabolizing enzyme polymorphisms and chemotherapy-related ovarian failure in breast cancer survivors

OBJECTIVE To determine if genetic variation in chemotherapy metabolism are associated with risk of ovarian failure in breast cancer patients after adjuvant chemotherapy. DESIGN Prospective cohort study. SETTING Comprehensive cancer center. PATIENT(S) Early-stage breast cancer patients who were premenopausal at cancer diagnosis and treatment. INTERVENTION(S) None. MAIN OUTCOMES MEASURE(S) Chemotherapy-related ovarian failure (CROF). RESULT(S) A total of 127 breast cancer subjects who were premenopausal at cancer diagnosis and underwent cyclophosphamide-based chemotherapy were genotyped for nine single-nucleotide polymorphisms (SNPs) in enzymes involved in cyclophosphamide activation (CYP3A4, CYP2B6, CYP3A5) and detoxification (GSTA1, GSTM1, GSTP1, GSTT1). Median age at chemotherapy was 43.2 years. Median follow-up after chemotherapy was 5.2 years. For the entire cohort, there was no significant association between CROF and SNPs. However, the association between CROF and SNPs was modified by age at chemotherapy. In subjects younger than 45 years old at chemotherapy, CYP3A4 *1B variants had significantly longer time to CROF than CYP3A4 *1A homozygotes in an adjusted multivariable Cox model. Age and tamoxifen use were also independently associated with CROF. CONCLUSION(S) A common SNP in a cyclophosphamide drug-metabolizing enzyme appears to be related to ovarian failure after cyclophosphamide-based chemotherapy in young women with breast cancer. Larger prospective studies to validate these results should be directed toward women younger than 45 years of age at chemotherapy.

Comparability of antimüllerian hormone levels among commercially available immunoassays

OBJECTIVE To compare antimüllerian hormone (AMH) levels among three commercially available AMH immunoassays: AMH Gen II (Beckman Coulter), Ultrasensitive AMH (Ansh Labs), and picoAMH (Ansh Labs). DESIGN Cross-sectional. SETTING Academic reproductive endocrinology program. PATIENT(S) 90 newly diagnosed breast cancer patients before cancer treatment. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Proportion of detectable AMH levels by immunoassay, and comparability among assays. RESULT(S) At a mean age of 38.1 years, the median (interquartile range) AMH level for the cohort was 0.92 [1.35] ng/mL for the Gen II assay, 1.68 [2.30] ng/mL for the Ultrasensitive assay, and 1.52 [2.41] ng/mL for the picoAMH assay. Significantly higher proportions of detectable AMH levels were observed with the picoAMH kit (97%) compared with both the Gen II (84%) and Ultrasensitive (92%) assays. Although the AMH results were highly correlated among the assays (r = 0.92-0.99), the Gen II AMH levels were consistently lower than both Ultrasensitive and picoAMH levels. Moreover, as AMH levels increased, the magnitude of difference grew larger between Gen II and each of the other two assays. CONCLUSION(S) Measurement of AMH levels with the picoAMH kit maximized detection at very low levels, particularly in contrast with the Gen II kit. Conversion of AMH levels from different immunoassays using regression equations is potentially highly inaccurate.

Experiencing reproductive concerns as a female cancer survivor is associated with depression

Young adult female cancer survivors have unmet reproductive concerns and informational needs that are associated with poorer quality of life. The purpose of this study was to examine the association between current reproductive concerns and moderate to severe depression among young survivors.

Ovarian imaging by magnetic resonance in adolescent girls with polycystic ovary syndrome and age-matched controls

To compare ovarian morphology in adolescent girls with and without polycystic ovary syndrome (PCOS) using magnetic resonance imaging (MRI).

Effect of Postdiagnosis Weight Change on Hot Flash Status Among Early-Stage Breast Cancer Survivors

PURPOSE Hot flashes (HF) affect a large proportion of breast cancer (BC) survivors and can negatively affect their quality of life. Treatments other than estrogen replacement to alleviate HF are needed. Body weight is related to hot flashes, but little is known about the effect of weight change on HF. PATIENTS AND METHODS We used data from 3,088 women previously treated for early-stage BC who were enrolled onto the Womens Healthy Eating and Living study to examine the association between weight change after a breast cancer diagnosis and the odds of reporting HF. RESULTS Overall, 36.1% of participants reported moderate to severe HF at study entry. At 2 years postdiagnosis, 69.2% of women remained within 10%, 4.8% lost at least 10%, and 26.0% gained at least 10% of their prediagnosis weight. Those who gained at least 10% of their prediagnosis weight had a greater risk of reporting HF than women who remained weight stable in that same period (odds ratio [OR], 1.33; 95% CI, 1.11 to 1.60; P = .003). Weight loss of at least 10% of prediagnosis weight was associated with a nonsignificant reduced risk (OR, 0.72; 95% CI, 0.47 to 1.08; P = .118) of reporting HF. However, the trend of weight change (weight loss and weight gain) on HF was significant both when examined categorically (P = .03) and continuously (P < .001). CONCLUSION Prevention of weight gain after a BC diagnosis-a modifiable behavior-may offer a viable intervention for relief of HF. Effects of intentional weight loss in BC survivors requires further study.