Chemotherapy-related Amenorrhea Research Articles

Relationship between reproductive history, anthropometrics, lifestyle factors, and the likelihood of persistent chemotherapy-related amenorrhea in women with premenopausal breast cancer

To determine the association between patient characteristics at diagnosis of premenopausal breast cancer, including gravidity, parity, age at menarche, age at first birth, alcohol use, smoking history, weight, height, and body mass index (BMI), with the development of persistent chemotherapy-related amenorrhea (CRA) in follow-up. Retrospective cohort study. Dana Farber Cancer Institute and Brigham and Women's Hospital. Premenopausal women with breast cancer. We identified all premenopausal women who received standard adjuvant chemotherapy during 1997-2005 for whom menstrual data were available. Multivariable logistic regression models evaluating persistent amenorrhea at ≥6 month after completion of chemotherapy were conducted. Persistent chemotherapy-related amenorrhea (CRA) at ≥6 months from completion of chemotherapy. A total of 431 women met eligibility criteria and had ≥6-months' follow-up. Women with older (>13 years) vs. younger (12-13 years) age at menarche were more than twice as likely to remain amenorrheic. Current smokers had 2.4 greater odds of CRA vs. never smokers, although this association was not statistically significant (95% confidence interval, 0.86-6.75). Few identifiable factors contribute to the variability in CRA among premenopausal women after adjuvant chemotherapy for breast cancer. Further research to improve the prediction of CRA, premature menopause, and infertility in young breast cancer survivors is warranted.

Prospective Evaluation of Ovarian Function in Women with Breast Cancer Treated with Anthracyclin-Based Chemotherapy with or without Docetaxel.

Abstract Background: to determine prospectively the incidence of chemotherapy-related amenorrhea and the recovery of ovarian function in premenopausal women with breast cancer undergoing adjuvant or neoadjuvant anthracyclin-based chemotherapy with or without docetaxel.Material and methods: we studied the incidence and the reversibility of clinical amenorrhea induced by different chemotherapy regimens: i) 6 cycles of 5-fluorouracil 500mg/m2, epirubicin 100mg/m2 and cyclophosphamide 500mg/m2 on day 1 every 3 weeks (6FEC) and ii) 3 cycles of FEC 100 followed by 3 cycles of docetaxel 100 mg/m2 on day 1 every 3 weeks (3FEC/3D) and iii) 4 cycles of FEC 100 followed by 4 cycles of docetaxel on day 1 every 3 weeks (4FEC100/4D) .Recovery of ovarian function was defined as recovery of premenopausal hormonal values :luteinizing hormone (LH <17mIU/ml),follicle-stimulating hormone (FSH <45.7mIU/Ml) and oestradiol (E2>50pg/ml).This recovery of ovarian function did not need to be associated with regular menses.Hormonal dosages were performed every 3 months starting at the beginning of chemotherapy and during the year following the end of chemotherapy.After, dosages were performed every 6 months.Results: 170 premenopausal patients were included between january 2005 and january 2008: 62 patients received 6FEC, 66 patients 3FEC/3D and 42 patients 4FEC/4D. The median age was 41 years (range: 25-51) in 6FEC, 42.8 years (range: 27-52.8) in 3FEC/3D and 40.2 years (range: 24-49.5)in 4FEC/4D. The incidence of chemotherapy-related amenorrhea at the end of chemotherapy was similar in the 3 groups: 90.3% in the 6FEC arm, 89.4% in the 3FEC/3D arm and 92.8% in the 4FEC/4D arm. However in the year following the end of chemotherapy, more patients recovered ovarian function in the 3FEC/3D arm (51.5%)(p=0.017) and in the 4FEC/4D arm (50%)(p=0.046)compared with the 6FEC group (30.6%). The difference was statisticaly significant for patients > or=40 years but not for patients < 40 years.Importantly, among the 23 patients with premenopausal hormonal values and treated with tamoxifen, 12/23 did not mention any menses recovery during the first year of follow-up.Conclusion: our prospective study confirms our previous retrospective data showing that 3FEC/3D and 4FEC/4D induce less definitive amenorrhea than 6FEC. Age is the most important predictor of ovarian function recovery, independently of chemotherapy regimen.Anamnestic data, especially in patients treated with tamoxifen are insufficient to determine pre-or postmenopausal status. Therefore, hormonal values must be followed regularly during and after chemotherapy. Since the menopausal status has an impact on the endocrine therapy choice. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2086.

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. 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.

Chemotherapy-related amenorrhea in premenopausalwomen with breast cancer

To report the incidence of chemotherapy-related amenorrhea (CRA) from chemotherapy with/without adjuvant endocrine therapy in premenopausal women with breast cancer and to analyze the related factors. From January 2000 to August 2006, 326 premenopausal women (<or=50 y old) who completed chemotherapy were available for analysis. The CRA definitional criterion in this study was no menstruation for 6 months in a woman who was premenopausal at diagnosis. As risk factors for CRA, woman's age, the type of chemotherapy regimen, adjuvant endocrine therapy use, and body mass index were evaluated. The median age was 42 years (range, 22-50 y). The median follow-up period was 37 months (range, 12-80 mo). Women were divided into two groups by age at diagnosis: 128 women in group 1 (less than 40 years old) and 198 women in group 2 (age >or=40 y). CRA occurred in a total of 223 (68%) women: 43% in group 1 and 85% in group 2 (P < 0.001). Despite CRA, 14% resumed menstruation: 24% in group 1 and 11% in group 2. Another 40 (12%) women had less than 6 months of menstruation interruption. Permanent CRA was related with age at diagnosis and use of adjuvant endocrine therapy (P < 0.05). In this study, there were four pregnancies, two of which resulted in therapeutic abortion due to ongoing chemotherapy. This study confirmed that the rate of CRA depends on age at diagnosis and the use of adjuvant endocrine therapy. It is essential to inform young women of reproductive age of the possibility of amenorrhea or resumption of menstruation and contraceptive options.

Anthracyclines: The First Generation of Cytotoxic Targeted Agents? A Possible Dream

Anthracyclines: The First Generation of Cytotoxic Targeted Agents? A Possible Dream

Chemotherapy related amenorrhea and hormonal measures of ovarian reserve in young breast cancer patients

OBJECTIVE: To determine if post-chemotherapy levels of anti-Mullerian hormone (AMH), inhibin B and follicle stimulating hormone (FSH) are associated with chemotherapy related amenorrhea (CRA) in breast cancer patients. To compare these hormones and stages of reproductive aging between breast cancer patients and age-matched healthy controls. DESIGN: Prospective cohort. MATERIALS AND METHODS: A cohort study 127 breast cancer patients with Stages I-III disease, premenopausal at diagnosis, were enrolled 1-4 years from chemotherapy. The primary endpoint was CRA (> 12 months of amenorrhea after chemotherapy). Cancer patients were age-matched to healthy controls. Menstrual patterns and clinical factors were collected prospectively. Bloods were assayed for hormones. Bivariable associations between AMH, inhibin B, FSH, demographics and chemotherapy regimen with CRA were assessed. Poisson regression models examined independent predictors of CRA and controlled for confounding. Matched pair analyses compared cancer to control subjects. RESULTS: Median age at chemotherapy was 43.2 (range 26.7-57.8). Median years of follow up since chemotherapy were 5.2 (range 0.4-7.6). At enrollment, 55% (70/127) of subjects had CRA. Compared to subjects without CRA, subjects with CRA had higher FSH and lower AMH and inhibin B even after controlling for confounders (all p<0.001). While most CRA subjects had undetectable levels of AMH (< 40 pg/mL), 42% had detectable AMH. Compared to controls, breast cancer subjects had significantly higher FSH and lower AMH and inhibin B (all p<0.001). Cancer subjects also had more advanced stages of reproductive aging compared to controls (p<0.001). Nine subjects (13%) with CRA at enrollment resumed menstrual bleeding. Compared to women who did not resume menstruating, these nine subjects were younger and were more likely to have had dose dense therapy. AMH, inhibin B and FSH at the time of enrollment did not predict resuming menses. CONCLUSIONS: AMH, inhibin B and FSH were significantly associated with CRA in breast cancer patients. Compared to age-matched controls, cancer patients had lower hormonal measures of ovarian reserve. Interestingly, a large proportion of CRA subjects had detectable levels of AMH, suggesting continued presence of ovarian follicles despite significant amenorrhea. These hormones did not predict resumption of menses after CRA. The utility of using these hormones for predicting CRA after cancer therapy is yet to be established.

Are cyclophosphamide drug metabolizing enzyme polymorphisms associated with ovarian failure after chemotherapy in young breast cancer patients?

OBJECTIVE: The objective was to determine if cyclophosphamide drug metabolizing enzyme polymorphisms are associated with ovarian failure in breast cancer patients after cyclophosphamide-based adjuvant chemotherapy. We hypothesized that breast cancer patients with drug metabolizing enzyme polymorphisms that result in higher cyclophosphamide exposure are more likely to develop chemotherapy related amenorrhea (CRA) after cyclophosphamide-based adjuvant chemotherapy. DESIGN: Prospective cohort. MATERIALS AND METHODS: We conducted a cohort study of 127 breast cancer patients with Stages I-III disease, premenopausal at diagnosis, enrolled 1 to 4 years from chemotherapy. All patients received cyclophosphomide-based chemotherapy. The primary endpoint was time to CRA (CRA defined as > 12 months of amenorrhea after chemotherapy start). Menstrual status and clinical factors were collected prospectively. DNA was extracted from enrollment bloods and used to genotype CYP2B6, CYP2C9, CYP2C9, CP3A4, CYP3A5, GSTA1, GSTM1, GSTT1 and GSTP1. Bivariable analyses assessed the association between 9 polymorphisms, demographic and chemotherapy regimen variables with CRA. Multivariable Cox proportional hazards regression models were developed to examine the independent predictors of time to CRA and to control for confounding. RESULTS: Median age at chemotherapy was 43.2 years (range 26.7-57.8). Median years of follow up since chemotherapy were 5.2 years (range 0.4-7.6). Age, taxane exposure/length of chemotherapy, dose dense therapy and tamoxifen were associated with higher risk of CRA. The association between time to CRA and polymorphisms appeared to be modified by age at chemotherapy (< 45 years), though these interactions did not reach statistical significance in this pilot study. After adjusting for clinical variables, CYP3A4∗1A/1B heterozygotes had significantly longer time to CRA than CYP3A4∗1A/∗1A homozygotes (HR 0.26 [95% CI 0.07-0.92]). Age and tamoxifen use were also independently associated with time to CRA. CONCLUSIONS: Cyclophosphamide drug metabolizing enzyme polymorphisms may aid in predicting risk of ovarian failure after cyclophosphamide-based chemotherapy in young women with breast cancer. Larger prospective studies in women less than 45 years of age at chemotherapy are needed to validate these results.

Efficacy of Nyoshinsan/TJ-67, a traditional herbal medicine, for menopausal symtoms following surgery and adjuvant chemotherapy for premenopausal breast cancer

We report a 39-year-old woman with premenopausal breast cancer who developed estrogen-deficiency symptoms associated with chemotherapy-related amenorrhea, and was successfully treated with Nyoshinsan/TJ-67, a Japanese traditional herbal medicine (Kampo). Six other breast cancer survivors with menopausal symptoms were also treated with Nyoshinsan/TJ-67, and five of the six patients showed noticeable improvement without adverse effects. Managing estrogen-deficiency symptoms in breast cancer survivors is still problematic, and Nyoshinsan/TJ-67 may be a useful and safe agent for such symptoms in these patients.

A Pilot Study of Predictive Markers of Chemotherapy-Related Amenorrhea Among Premenopausal Women with Early Stage Breast Cancer

Background: Premenopausal women treated for early stage breast cancer (ESBC) are at risk for chemotherapy-related amenorrhea (CRA). Prospectively-validated, predictive markers of CRA are needed. Patients and Methods: Premenopausal women with ESBC and planned chemotherapy (≥ 25% risk of amenorrhea) were evaluated. Follicle stimulating hormone (FSH), estradiol, Inhibin A and B, anti-Müllerian hormone (AMH), and quality of life (QOL) were prospectively evaluated pre-, post-, 6 months and 1 year post-chemotherapy and correlated with age and menstrual status. CRA was defined as absence of menses 1 year post-chemotherapy. Results: Forty-four women were evaluated at the time of analysis. Median age at diagnosis and FSH 1 year post-chemotherapy were higher among women with CRA (44 yrs [33–51] vs. 40 yrs [31–43]; p = 0.03; 39.8 vs. 5.0 mLU/mL, p = 0.0058, respectively). Median estradiol 1 year post-chemotherapy was higher among women who resumed menses (108.3 vs. 41.3 pg/mL, p = 0.01). Pre-chemotherapy median Inhibin B and AMH were lower among women with CRA (33.2 vs. 108.8 pg/mL; p = 0.03; 0.16 vs. 1.09 ng/mL, p = 0.02, respectively). The risk of CRA was increased among women with lower pre-chemotherapy Inhibin B (RR = 1.67, p = 0.15) and AMH (RR = 1.83, p = 0.05). Amongst women whose pre-chemotherapy Inhibin B and AMH values were below the median, the incidence of CRA was 87.5%. Conclusions: Results indicate that pre-chemotherapy Inhibin B and AMH are lower among women experiencing CRA and may be predictive of CRA among premenopausal women facing chemotherapy for ESBC.

Relationships between clinical and biochemical predictors of chemotherapy-related amenorrhea in premenopausal adjuvant breast cancer patients

11011 Background: Premature ovarian failure (POF) is a major side effect of breast cancer adjuvant therapy. Predicting post- chemotherapy POF and reproductive status impacts decisions about fertility, contraception, menopausal issues and breast cancer treatment. We examined clinical and biochemical predictors of chemotherapy related amenorrhea (CRA) in premenopausal adjuvant breast cancer patients. Methods: We conducted a cohort study of 121 breast cancer patients with stages I-III disease, premenopausal at diagnosis, enrolled 1 to 4 years from chemotherapy. All patients received 4 cycles of doxorubicin and cyclophosphomide with or without 4 cycles of paclitaxel or docetaxel, at q2 (dose-dense) or q3 week intervals. The primary endpoint was CRA (amenorrhea &gt; 12 months from chemotherapy start). Pretreatment menstrual status and clinical factors were collected prospectively; subjects were recontacted for additional information and venipuncture. Regression models were used to examine risk factors for CRA and log FSH. Results: Mean age was 43.2 years (range 26.7–57.8). Mean follow up from chemotherapy start to enrollment was 2.1 years (range 1.0–4.1). 68 subjects developed CRA, while 53 continued menstruating. In a model including age, tamoxifen use, dose density, chemotherapy regimen, ovarian suppression during chemotherapy, smoking, body mass index and race, only age (OR 1.57[CI 1.29–1.89], p&lt;0.001), tamoxifen use (OR 7.25 [CI 5.89–34.87], p=0.01), and dose density (OR 3.38 [CI 1.16–16.50], p=0.03) had independent associations with CRA. Serum FSH at enrollment (n=112) was higher in CRA than in non-CRA (11.8 vs 45.8, p&lt; 0.001). However, 39% (25/65) of CRA subjects had FSH &lt; 40 mIU/mL, the biochemical threshold for menopause (mean 26.4, range 10.1–39.9). FSH was not associated with chemotherapy regimen (p=0.51) or schedule (p=0.21). Conclusions: Age, tamoxifen use, dose density and subsequent FSH were independently associated with CRA. Clinically, amenorrhea for more than 12 months did not always represent biochemical menopause. Better methods are needed to characterize ovarian function in patients after adjuvant chemotherapy. No significant financial relationships to disclose.

Fertility and adjuvant treatment in young women with breast cancer

Women of childbearing age with breast cancer are often concerned about whether they will become infertile after treatment, and for those who wish to bear children, whether a subsequent pregnancy will alter their risk of disease recurrence. The risk of chemotherapy-related amenorrhea (CRA), menopause, and infertility appear to be related to patient age and type of treatment received, though data regarding actual fertility following treatment are limited. There are options available for fertility preservation for young women who wish to have a biologic child after breast cancer and are at risk for infertility. Options include cryopreservation of embryos, oocytes, ovarian tissue prior to treatment, and ovarian suppression through chemotherapy. However, most of these are considered experimental, and there are limited data regarding the safety of such strategies. There has been concern that pregnancy after breast cancer may worsen prognosis in light of the endocrine manipulations used to treat breast cancer, particularly for women with hormone sensitive disease. Several studies addressing the potential risk of pregnancy after breast cancer have not revealed any negative effect on prognosis. However, these studies have significant limitations, and concerns about a negative impact for some remain. Ongoing and future prospective studies evaluating fertility and pregnancy issues for young breast cancer survivors are warranted for this vulnerable population facing this difficult issue.

Chemotherapy-Related Amenorrhea (CRA) among Premenopausal Patients Treated for Acute Leukemia.

Background: Little is known about the late effects of treatment for acute leukemia on ovarian function. We sought to evaluate the rate of long-term chemotherapy-related amenorrhea (CRA) among premenopausal women treated for acute leukemia.Methods: The Cleveland Clinic database of patients treated for acute leukemia between July 1994 and July 2005 was searched for patients aged 15–44 at diagnosis who were believed to be alive. Thirty of 69 identified patients were excluded due to active disease, on-going treatment or lost to follow-up. Questionnaires regarding menstrual and fertility history were mailed to the remaining 39 patients.Results: Twenty-five patients responded to the questionnaire, 4 of whom were excluded due to lack of menses at the time of diagnosis (n=2), use of Depo-provera at time of diagnosis (n=1) or use of Depo-provera at time of f/u (n=1). The median age of the remaining 21 patients was 30 (range 15 to 44). Thirteen patients had AML and 8 had ALL. Nine of the 21 had undergone myeloablative transplant, 8 allogeneic and 1 autologous. Median f/u time from treatment was approximately 43 months (range 9 to 141). Long-term CRA occurred in 8/21 patients (38%). Only 2/12 patients (17%) who received standard-dose chemotherapy alone had persistent CRA while 6/9 (67%) of those undergoing transplant had persistent CRA (p=0.032, Fisher's Exact test). The incidence of CRA increased with age: 0/3 patients under age 18, 1/4 patients age 18–25, and 7/14 patients age 26–44 at treatment remained amenorrheic (p=0.042, 1-sided Cochran-Armitage test). Only 2 patients reported attempts at fertility following treatment. One patient reported delivering three children, the other patient was amenorrheic and was undergoing fertility treatment.Conclusions: These findings suggest that a substantial minority of young survivors of acute leukemia will experience premature ovarian failure. Increasing age at treatment and transplant are associated with a greater risk of long-term CRA.

P-166: Chemotherapy-related amenorrhea in premenopausal women with breast cancer: The effect of paclitaxel, dose density and trastuzumab

The effect of the addition of paclitaxel (T) to adriamycin and cyclophosphamide (AC), use of a dose dense (DD, q2wk) regimen, or use of trastuzumab/herceptin (H) on menstrual functioning in premenopausal women with early breast cancer remains uncertain. No previous studies have evaluated the effects of DD and H on the menstrual cycle.

Chemotherapy-related amenorrhea in women with early breast cancer: The effect of paclitaxel or dose density

10506 Background: The effect of the addition of paclitaxel (T) to adriamycin and cyclophosphamide (AC), or dose density (DD, q2wk) on menstrual functioning in women with early breast cancer remains uncertain. Methods: We reviewed data from premenopausal women treated at Dana-Farber Cancer Institute and Brigham and Women’s Hospital who received adjuvant chemotherapy with either AC or AC-T from 1997–2005 for whom pre- and post-treatment menstrual data were available. A multivariable logistic regression model evaluating amenorrhea at 6 months or greater follow-up was conducted. Results: Of the 403 patients eligible for analysis, average age at diagnosis was 41 years (range 25–50); average weight was 67kg; 10% were smokers, 53% had never smoked; 24% were nulliparous. 60% of women received AC, 40% AC-T; 20% of women received DD therapy (either AC or AC-T); 72% received tamoxifen. The multivariable model adjusting for age, weight, gravity, parity, smoking, alcohol use, and tamoxifen use, revealed that risk of amenorrhea was not statistically different in patients receiving AC-T versus AC (OR = 1.45, 95% CI 0.78–2.69) or in patients receiving DD therapy versus standard (OR = 1.61, 95% CI 0.74–3.49). However, a planned future analysis including data from an additional 200+ patients may yield significant differences. Age directly correlated with risk of amenorrhea, OR = 1.40, 95% CI 1.30–1.50) for every year increase in age, and women receiving tamoxifen were more likely to be amenorrheic (OR = 1.99, 95% CI 1.05–3.79). Conclusions: The addition of T to AC or use of DD therapy does not appear to increase the likelihood of amenorrhea in follow-up. These findings may assist premenopausal women with breast cancer when making decisions at diagnosis and in follow-up. No significant financial relationships to disclose.

Inadvertent Use of Aromatase Inhibitors in Patients with Breast Cancer with Residual Ovarian Function: Cases and Lessons

Aromatase inhibitors (AIs) are important adjunctive therapy for postmenopausal women with hormone receptor— positive, early-stage breast cancer. At the present time, AIs have no role for the management of breast cancer in premenopausal women. We report on several cases of the inadvertent use of AI therapy among women with residual ovarian function. A common experience in these cases was the onset of chemotherapy-related amenorrhea before initiation of AI therapy, which confounded assessment of true menopausal status. We believe clinicians should be aware of the potential ovarian reserve among women with treatment-related amenorrhea so as to avoid use of AI therapy in patients in whom there is uncertainty about menopausal status.

Incidence of chemotherapy‐induced, long‐term amenorrhea in patients with breast carcinoma age 40 years and younger after adjuvant anthracycline and taxane

Twenty-five percent of all women with breast carcinoma are premenopausal and are at risk for chemotherapy-induced menopause with long-term side effects. Although there is considerable documentation of the rates of chemotherapy-induced amenorrhea with classic adjuvant regimens, there are inadequate data that address the impact of taxanes on menstrual function in this setting. The objective of this analysis was to determine the incidence of long-term amenorrhea (> or = 12 mos) in women with breast carcinoma age 40 years and younger after adjuvant anthracycline and taxane-based chemotherapy, with or without subsequent tamoxifen. The authors identified 235 premenopausal women with breast carcinoma age 40 years or younger who were treated with adjuvant anthracycline and taxane-based chemotherapy at Memorial Sloan-Kettering Cancer Center from January 1997 to June 2003. One hundred sixty-six patients met all eligibility criteria and had sufficient follow-up for evaluation. The median age of patients at diagnosis was 36 years (range, 27-40 yrs). All patients had regular pretreatment menses, 25 patients (15%) developed long-term amenorrhea, and 141 patients (85%) resumed menstruation. Eighty-two patients (49%) also received tamoxifen: The incidence of amenorrhea among them was 17%. There was a statistically significant association between age and the development of amenorrhea, with older women at higher risk (P < 0.01). The sequential addition of a taxane to standard adjuvant anthracycline-based chemotherapy did not appear to produce a high rate of chemotherapy-related amenorrhea compared with historic controls. To increase the information available to assist young patients who are considering adjuvant therapy, prospective studies should incorporate menstrual function ascertainment by patient-reported history and assays of ovarian function.

Ovarian function in premenopausal women treated with adjuvant chemotherapy for breast cancer.

Adjuvant chemotherapy for breast cancer causes significant changes in ovarian function. More young women survive breast cancer than ever before and they are at risk of the sequelae of early menopause. We attempted to (1) define menopausal status in the setting of adjuvant chemotherapy; (2) define chemotherapy-related amenorrhea (CRA); (3) document rates of permanent amenorrhea, temporary amenorrhea, and oligomenorrhea among different regimens; and (4) analyze variables that influence ovarian function. We reviewed reports of the effects of adjuvant chemotherapy for breast cancer on ovarian function in premenopausal women. We searched Medline and Cancerlit from 1966 to 1995 on the following terms: breast neoplasms; chemotherapy, adjuvant; menstruation disorders; premature menopause, and amenorrhea. Further references were obtained from reports retrieved in the initial search. A uniform definition of menopause and CRA is lacking. The wide range of CRA rates reported in adjuvant chemotherapy trials is a result, at least in part, of this problem. The average CRA rate reported in regimens based on cyclophosphamide, methotrexate, and fluorouracil (CMF) is 68% (95% confidence interval [CI], 66% to 70%), with a range of 20% to 100%. CRA incidence varies with age, cytotoxic agent, and cumulative dose. Ovarian damage is the most significant long-term sequela of adjuvant chemotherapy in premenopausal breast cancer survivors. We suggest a common definition of the following important terms: menopausal status, CRA (early and late), temporary CRA, and oligomenorrhea in the setting of adjuvant treatment. With uniform definitions in place, regimens can be more precisely compared with respect to this important complication.