ABSTRACT: 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.
Breast cancer patients (n = 127) with American Joint Committee on Cancer stage I to III disease who were premenopausal at diagnosis were enrolled postchemotherapy and observed. The primary endpoint was chemotherapy-related amenorrhea (CRA) (> or = 12 months of amenorrhea after chemotherapy). Matched pair analyses compared AMH, inhibin B, and follicle-stimulating hormone (FSH) levels between cancer and age-matched control subjects. Associations between hormones, CRA status, and change in CRA status over time were assessed.
The median age of the patients at chemotherapy was 43.2 years (range, 26.7-57.8 years). At enrollment, median follow-up since chemotherapy was 2.1 years, and 55% of subjects had CRA. Compared with age-matched controls, cancer subjects had significantly lower AMH (P = .004) and inhibin B (P < .001) and higher FSH (P < .001). AMH (P = .002) and inhibin B (P = .001) were found to be significantly associated with risk of CRA, even after controlling for FSH. AMH was significantly lower (P = .03) and FSH was significantly higher (P = .04) in menstruating subjects who developed subsequent CRA.
AMH and inhibin B are 2 additional measures of postchemotherapy ovarian function in late reproductive-aged breast cancer survivors. With further research and validation, these hormones may supplement limited current tools for assessing and predicting postchemotherapy ovarian function.
Cancer 11/2009; 116(3):592-9. · 4.77 Impact Factor
ABSTRACT: To determine if genetic variation in chemotherapy metabolism are associated with risk of ovarian failure in breast cancer patients after adjuvant chemotherapy.
Prospective cohort study.
Comprehensive cancer center.
Early-stage breast cancer patients who were premenopausal at cancer diagnosis and treatment.
Chemotherapy-related ovarian failure (CROF).
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.
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.
Fertility and sterility 05/2009; 94(2):645-54. · 3.97 Impact Factor
ABSTRACT: Image-guided treatment planning that minimizes irradiation of critical lymph nodes (LNs) may reduce the incidence and severity of long term complications following breast cancer treatment. This localization cannot be obtained with conventional imaging techniques and we undertook this proof of concept study to determine whether a coordinated use of SPECT and CT has sufficient precision to inform radiation planning and potentially lessen the incidental exposure of critical LNs. Thirty-two consecutive women with breast cancer were injected in the arm ipsilateral to their breast cancers prior to radiation treatment with 0.5 mCi of filtered (99m)Tc-sulfur colloid and underwent scanning with a hybrid device which combined a dual-head SPECT camera and a low-dose, single slice CT scanner. The number of visualized LNs as well as their locations, maximum counts, and total uptake were recorded. Coordinates derived from the SPECT/CT fusion images were used to map LN locations onto the 3D radiation treatment planning system. A mean of 3.4 (SD 2.0) lymph nodes were detected in each subject. Level I and II LNs were detected more often in patients who had sentinel node biopsies, and more supraclavicular nodes were detected in patients who had undergone axillary dissection (P < 0.001). SPECT-CT derived LN coordinates were successfully mapped onto radiation simulation CT scans for all patients. SPECT/CT fusion images localize the LNs draining the arm after breast cancer surgery. These finding suggest that SPECT/CT may be helpful in minimizing incidental LN irradiation and in directing breast cancer therapy to reduce long-term morbidity.
Breast Cancer Research and Treatment 01/2009; 116(3):531-8. · 4.43 Impact Factor