At present, there is no gold standard test for the investigation of ovarian function in pre-menopausal breast cancer patients who develop amenorrhea after chemotherapy. Clinical, biochemical and biophysical investigations continue to be utilized in clinical practice, despite concerns regarding their predictive value for menopause. The resulting uncertainty about a woman's actual menopausal status has important consequences for patient management. These include choice of appropriate endocrine therapy, assessment of residual ovarian function and its effect on breast cancer recurrence, fertility issues and the prediction of the likelihood of conception. It is hoped that the development of novel surrogates may allow clinicians to more accurately assess menopausal status and thereby facilitate tailored and individualised therapy for this common group of patients.
[Show abstract][Hide abstract] ABSTRACT: The authors sought to describe the age-specific impact of infertility and early menopause after chemotherapy among reproductive age women with cancer.
A total of 1041 women diagnosed with cancer between the ages of 18 and 40 years responded to a retrospective survey on reproductive health history. Five cancer types were included: leukemia, Hodgkin disease (HD), non-Hodgkin lymphoma (NHL), breast cancer, and gastrointestinal(GI) cancer. Survey questions addressed acute ovarian failure (cessation of menses after treatment), early menopause (menopause before 45 years old), and infertility (failed conception). Logistic regression was used to determine the proportions of acute ovarian failure and infertility based on age at diagnosis. Censored data methods were used to determine the probability of early menopause.
Six hundred twenty women received chemotherapy alone. The percentage reporting acute ovarian failure was 8%, 10%, 9%, and 5% for HD, NHL, breast cancer, and GI cancer, respectively. Acute ovarian failure increased significantly with age at diagnosis (P < .05). In subjects not reporting acute ovarian failure, the incidence of infertility was at least 40% at age 35 years and increased significantly with age at diagnosis in HD and breast cancer (P < .05). The estimated probability of early menopause was at least 25% at age 30 years and increased significantly with younger age at diagnosis in HD, NHL, and GI cancer (P < .05).
For patients to receive appropriate counseling, it is important that they understand the potential increased risk of infertility and early menopause beyond that of acute ovarian failure. These findings can provide improved, age-specific counseling regarding reproductive impairment for young women diagnosed with cancer.
Cancer 04/2012; 118(7):1933-9. DOI:10.1002/cncr.26403 · 4.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Fulvestrant is an endocrine agent which degrades the estrogen receptor, thereby downregulating its signaling. Trials of fulvestrant are limited by inconsistent study populations and drug dosing. The optimal use of fulvestrant in advanced breast cancer is therefore unclear.
A systematic review of electronic databases was conducted to identify randomized trials of fulvestrant versus other endocrine therapy. The hazard ratios (HR) for time to progression (TTP) and the odds ratios (OR) for serious adverse events (SAEs), discontinuation of treatment due to toxicity and commonly reported toxicities (hot flashes, venous thrombosis, gastrointestinal disturbance, arthralgia, and asthenia) were pooled in a meta-analysis. Meta-regression explored heterogeneity in study population and fulvestrant dosing.
Eight studies were included in the analysis. Overall, there was no difference in TTP between fulvestrant and control groups (HR: 0.94, p=0.18). On meta-regression, fulvestrant showed reduced hazards for TTP compared to aromatase inhibitors (AI) if used in first line, in studies where fewer patients received adjuvant endocrine therapy and at higher doses. Rates of SAEs and treatment discontinuation were similar for fulvestrant and control groups, but fulvestrant monotherapy was associated with significantly less arthralgia (OR: 0.73, p=0.02). The addition of fulvestrant to AI was not associated with improved TTP, but led to increased toxicity.
In unselected patients, fulvestrant monotherapy is associated with similar efficacy, but reduced arthralgia compared with other endocrine therapy options. Use of high dose fulvestrant monotherapy in first line or in patients with limited prior exposure to adjuvant endocrine therapy may delay progression compared with AI.
Cancer Treatment Reviews 04/2013; 39(7). DOI:10.1016/j.ctrv.2013.03.004 · 7.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The reproductive sequelae of cancer treatments may provide an important model of accelerated ovarian aging. Tens of thousands of women treated for cancer each year experience infertility and early menopause as a result of treatment. A spectrum of reproductive compromise commonly ranges from immediate menopause at the time of cancer treatment to the less proximate outcome of early menopause in the years to decades after treatment. A woman's reproductive lifespan can be shortened after chemotherapy or radiation because such treatments likely decrease the number of viable eggs after treatment. This acceleration in the decline of the number of follicles leads to increased rates of not only infertility and miscarriage but also early menopause, which represents the most extreme form of accelerated ovarian aging. The degree of reproductive impairment is dependent on chronologic age and the diagnosis or treatment. The variation in outcomes that persist may be partially explained by pretreatment ovarian reserve. Establishing the use of clinical predictors such as ovarian reserve markers to effectively anticipate such outcomes is an obvious and important keystone in the foundation of cancer survivorship research. An improved understanding of cancer treatment's ability to accelerate follicle death, decrease fecundability, and initiate an earlier menopause could provide a clinically relevant, time-shortened, and reproducible snapshot into the basic biology of ovarian aging.
Seminars in Reproductive Medicine 11/2013; 31(6):462-468. DOI:10.1055/s-0033-1356482 · 2.35 Impact Factor
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