Chemotherapy-induced Amenorrhea Research Articles

Chemotherapy-induced amenorrhea (CIA) risk associated with taxane/platinum-based chemotherapy in young (≤45 years) breast cancer patients.

9592 Background: Twenty-five percent of women with breast cancer (BC) are premenopausal and 15% are diagnosed in reproductive age group (≤45 years), thus at risk of CIA. Although CIA rates with alk...

The role of BMI and age in chemotherapy-induced amenorrhea (CIA) in premenopausal breast cancer (PBC) patients treated with adjuvant FEC100 with or without docetaxel (D).

e12000 Background: Transitory or definitive amenorrhea (A) is a related side effect, specifically affecting young women diagnosed with breast cancer and treated with adjuvant chemotherapy (CT). Pre...

What lies behind chemotherapy-induced amenorrhea for breast cancer patients: a meta-analysis

To evaluate the incidence of chemotherapy-induced amenorrhea (CIA) and its therapeutic impact in premenopausal breast cancer patients. A systematic search was performed to identify clinical studies that compared the incidence of CIA with different chemotherapy regimens and oncological outcomes with and without CIA. The fixed-effects and random-effects models were used to assess the pooled estimates. Heterogeneity and sensitivity analyses were performed to explore heterogeneity among studies and to assess the effects of study quality. A total of 15,916 premenopausal breast cancer patients from 46 studies were included. The cyclophosphamide-based regimens, taxane-based regimens, and anthracycline/epirubicin-based regimens all increased the incidence of CIA with pooled odds ratios of 2.25 (95 % CI 1.26-4.03, P = 0.006), 1.26 (95 % CI 1.11-1.43, P = 0.0003) and 1.39 (95 % CI 1.15-1.70, P = 0.0008), respectively. The three-drug combination regimens of cyclophosphamide,anthracycline/epirubicin, and taxanes (CAT/CET) caused the highest rate of CIA compared with the other three drug combinations (OR 1.41, 95 % CI 1.16-1.73, P = 0.0008). Tamoxifen therapy was also correlated with a higher incidence of CIA, with an OR of 1.48. Patients with CIA were found to exhibit better disease-free survival (DFS) and overall survival (OS) compared with patients without CIA. With respect to molecular subtype, this DFS advantage remained significant in hormone-sensitive patients (HR 0.61, 95 % CI 0.52-0.72, P < 0.00001). The current meta-analysis has demonstrated that anthracycline/epirubicin, taxanes, cyclophosphamide, and tamoxifen all contributed to elevated rates of CIA, and CIA was not merely a side effect of chemotherapy but was a better prognostic marker, particularly for ER-positive premenopausal early-stage breast cancer patients. However, this topic merits further randomized control studies to detect the associations between CIA and patient prognosis after adjusting for age, ER status, and other influential factors.

Reply to K.-D. Yu et al

Reply to K.-D. Yu et al

Survival Benefit From Response-Guided Approach: A Direct Effect of More Effective Cytotoxic Regimens or an Indirect Effect of Chemotherapy-Induced Amenorrhea?

Survival Benefit From Response-Guided Approach: A Direct Effect of More Effective Cytotoxic Regimens or an Indirect Effect of Chemotherapy-Induced Amenorrhea?

Abstract P3-09-19: A prospective study of fertility preservation by controlled ovarian hyperstimulation (COH) without letrozole in young breast cancer patients before adjuvant chemotherapy: Preliminary results

Abstract Background: 6300 new cases of breast cancer arise in young women under 40 each year in France. The majority receives chemotherapy and a lot of them have not completed their family. The incidence of persistent chemotherapy-induced amenorrhea in these patients is approximately 20%. The incidence of infertility, although poorly studied, is probably higher. Besides, there has been a development of techniques of fertility preservation and henceforth physicians have to systematically offer these techniques to these young patients before the onset of chemotherapy. Few studies have addressed the issue of COH for fertility preservation in breast cancer pts. In most of these, letrozole is required during COH in order to limit the estrogen levels increase. In France, the use of letrozole in this specific area is not allowed. The aim of this prospective observational study is to evaluate the benefit/risk of the ovarian stimulation without letrozole for oocyte/embryo freezing in young breast cancer pts undergoing adjuvant chemotherapy. Methods: 28 young breast cancer patients were referred for fertility preservation before chemotherapy. Inclusion criteria were age 18 to 38, histologically confirmed invasive breast carcinoma, absence of metastases. 12 patients (6 due to a neoadjuvant setting and 6 because of the wishes of the patient) had only a follow up of their ovarian reserve. The 16 others patients were in an adjuvant setting and were asking for a fertility preservation. These 16 patients underwent COH during the interval between complete surgery and start of adjuvant chemotherapy. To reduce the risk of ovarian hyperstimulation, ovarian stimulation protocol will use gonadotropins and a GnRH antagonist and a GnRH agonist will do the ovulation trigger. All the patients were then enrolled in a systematic oncologic and reproductive follow-up for 2 consecutive years after the end of chemotherapy. All patients gave their informed consent for COH, egg/embryo freezing and follow-up. Results: Mean age of the study population was 31 years (25-37). Histologic type was invasive ductular carcinoma in all cases, except 1 medullary carcinoma. 14 tumours were hormonal receptors positive, 4 were Her 2 positive. 14 patients had not yet children. Mean initial AMH levels and AFC were respectively 17 (7,7-120) and 21(6-68). Length of stimulation was 12.5 (11-16). Time between surgery and chemotherapy was 46 days (19-95). Time between first consultation in the fertility preservation center and chemotherapy was 25 days (2-73). The mean number of vitrified oocytes was 6,2 (0-14). The mean number of frozen embryo was 2,8 (0-8). Mean duration of follow-up after the end of chemotherapy was 265 days (27-585). To date, no oncologic adverse effects were observed during the study period. Conclusion: These preliminary results confirmed the feasibility of a collaboration between oncologists, reproductive medicine doctor and biologist to allow all the women concerned to have access to a preservation of their fertility. Safety and results of COH had to be confirmed in a larger population. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-09-19.

Abstract P3-08-18: Association of tamoxifen use and ovarian aging in patients with invasive or pre-invasive breast cancer

Abstract Background: The use of tamoxifen has been shown to delay the recovery of chemotherapy-induced amenorrhea, however the independent impact of long-term endocrine therapy on ovarian aging is not known, and to our knowledge, has never been directly investigated. Understanding the effect of endocrine therapy on ovarian aging will help breast cancer patients of reproductive age make more informed and empowered decisions regarding their treatment. The aim of this study is to explore the relationship between tamoxifen therapy and age onset of menopause. Methods: We conducted a retrospective cohort study using patients identified through the UCSF Cancer Registry and UCSF SPORE database. Women who were diagnosed with Stage 1-3 invasive or in situ breast cancer between 1985 and 2011, who were premenopausal at the time of diagnosis and who did not receive systemic chemotherapy were included. Patients with recurrent disease and prior ovarian surgery were excluded. Eligibility was confirmed by telephone, and online or paper surveys were distributed to eligible subjects only. Age onset of menopause was the primary endpoint of the study and was defined as the age at which a woman had her last period and no menses for 12 months. Age onset of menopause was assessed through surveys. The primary analysis compared age onset of menopause between subjects who received tamoxifen for any duration and control subjects who never received tamoxifen. Secondary analyses were performed using a Cox proportional hazards model to determine whether duration of tamoxifen exposure and age of tamoxifen initiation impacted age onset of menopause in subjects treated with tamoxifen. Results: A total of 1137 potential subjects believed to meet eligibility criteria were identified and called, and 649 subjects were reached. Eligibility was confirmed by phone in 340 subjects. A total of 336 subjects consented to participate in the study, and 262 (78%) completed and returned the survey. 227 subjects were included in the primary analysis of which 110 subjects received prior tamoxifen, and 117 subjects received no prior tamoxifen. At the time of the survey, 16.3% vs. 20.2% of patients under age 50 that were exposed and not exposed to tamoxifen entered menopause, respectively. The median age onset of menopause was 50.94 and 51.34 for the tamoxifen and no tamoxifen groups, respectively. The hazard ratio between these groups was 1.077 which was not statistically significant (p = 0.6917). No association (p = 0.55) was found between the duration of tamoxifen use and the age onset of menopause. When controlling for tamoxifen duration, there was no significant difference (p = 0.93) in age onset of menopause between subjects who initiated tamoxifen prior to age 45 and those who initiated at age 45 or older. Conclusion: These data suggest that tamoxifen alone is not associated with an earlier age onset of menopause, and that tamoxifen use, in the absence of systemic chemotherapy, is unlikely to significantly accelerate ovarian aging. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-08-18.

Chemotherapy-induced amenorrhea in patients with breast cancer with a BRCA1 or BRCA2 mutation.

To determine the likelihood of long-term amenorrhea after treatment with chemotherapy in women with breast cancer who carry a BRCA1 or BRCA2 mutation. We conducted a multicenter survey of 1,954 young women with a BRCA1 or BRCA2 mutation who were treated for breast cancer. We included premenopausal women who were diagnosed with invasive breast cancer between 26 and 47 years of age. We determined the age of onset of amenorrhea after breast cancer for women who were and were not treated with chemotherapy, alone or with tamoxifen. We considered chemotherapy-induced amenorrhea to have occurred when the patient experienced ≥ 2 years of amenorrhea, commencing within 2 years of initiating chemotherapy, with no resumption of menses. Of the 1,426 women who received chemotherapy, 35% experienced long-term amenorrhea. Of the 528 women who did not receive chemotherapy, 5.3% developed long-term amenorrhea. The probabilities of chemotherapy-induced amenorrhea were 7.2% for women diagnosed before age 30 years, 33% for women age 31 to 44 years, and 79% for women diagnosed after age 45 years (P trend < .001). The probability of induced amenorrhea was higher for women who received tamoxifen than for those who did not (52% v 29%; P < .001). Age at treatment and use of tamoxifen are important predictors of chemotherapy-induced amenorrhea in women who carry a BRCA1 or BRCA2 mutation. The risk of induced long-term amenorrhea does not seem to be greater among mutation carriers than among women who do not carry a mutation.

Incidence of Chemotherapy-Induced Amenorrhea in Premenopausal Women Treated With Adjuvant FOLFOX for Colorectal Cancer

BackgroundStudies indicate that the incidence of young women diagnosed with colorectal cancer is rising, thus there is an increasing number of female colorectal cancer survivors of premenopausal and child-bearing age. Adjuvant FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) chemotherapy is the most widely used standard treatment for stage III and high-risk stage II colon cancer. We evaluated the incidence of FOLFOX-induced amenorrhea in women age 50 and younger treated with adjuvant therapy for colorectal cancer. Patients and MethodsA search of pharmacy records identified 119 women age 50 or younger who received adjuvant FOLFOX chemotherapy at Memorial Sloan-Kettering for stage II or III colorectal cancer from January 2002 and January 2011. Eligible patients were mailed an anonymous questionnaire. The returned surveys were reviewed and the results tallied. ResultsSeventy-three patients returned the questionnaire. Twenty-four patients were excluded from analysis: 19 were treated with pelvic radiotherapy, 2 patients had undergone bilateral oophorectomy, 2 had a hysterectomy, and 1 stopped menstruating before diagnosis. Forty-nine patient responses were analyzed. In total, 41% (n = 20) experienced amenorrhea during chemotherapy. Sixteen percent had persistent amenorrhea 1 year after completion of chemotherapy. The incidence of amenorrhea during chemotherapy trended higher in patients aged older than 40 compared with patients aged 40 and younger (59% vs. 31% [P = .075]). There was no statistically significant difference in persistent amenorrhea between the 2 age groups (24% vs. 13%; P = .42). ConclusionIn this retrospective series, there appears to be a trend toward FOLFOX induced amenorrhea during chemotherapy increasing with age. Twenty-four percent of women older than the age of 40 were found to have persistent amenorrhea after FOLFOX therapy. Because of the small sample size, the study is underpowered to detect a statistically significant difference between older and younger patients. Prospective studies are planned to further characterize the effect of FOLFOX on early menopause and fertility.

Chemotherapy-induced amenorrhea, menopause-specific quality of life, and endocrine profiles in premenopausal women with breast cancer who received adjuvant anthracycline-based chemotherapy: a prospective cohort study

We conducted a prospective observational study for premenopausal women receiving adjuvant adriamycin and cyclophosphamide-containing regimens to define the pattern of chemotherapy-induced amenorrhea (CIA), the menopause-specific quality of life (MENQOL), and the hormone profiles. From October 2003 to July 2007, 387 patients with breast cancer who underwent curative surgery were prospectively included. Patient self-assessment by MENQOL questionnaires and blood samples for hormone assays were taken before chemotherapy, and 1, 6, and 12months after chemotherapy was completed. Patients were categorized into three groups according to their duration and reversibility of amenorrhea, with 312 eligible patients split into long-term CIA (n=180, 57.7%), temporary CIA (n=113, 36.2%), and menstrual irregularity (n=19, 6.1%) groups. Risk factors for long-term CIA were identified as age ≥40years (p<0.001), the addition of taxane (p=0.01), and tamoxifen use (p=0.03). MENQOL was worst immediately after the completion of adjuvant chemotherapy, and this was not fully recovered even 12months after chemotherapy had finished. Age ≥40years and tamoxifen exposure were inversely associated with MENQOL. In long-term CIA patients, the level of follicle-stimulating hormone increased after chemotherapy; this level, however, was reduced in patients who received tamoxifen, but remained high and stable in those who did not (p<0.001 at 6months; p<0.001 at 12months). This study showed that most premenopausal breast cancer patients who received adjuvant chemotherapy experienced clinically significant CIA, followed by impaired MENQOL. Our findings may be relevant in the decision-making processes for premenopausal women with breast cancer.

Chemotherapy-induced amenorrhea: a prospective study of brain activation changes and neurocognitive correlates

Chemotherapy-induced amenorrhea (CIA) often occurs in pre- and peri-menopausal BC patients, and while cancer/chemotherapy and abrupt estrogen loss have separately been shown to affect cognition and brain function, studies of the cognitive effects of CIA are equivocal, and its effects on brain function are unknown. Functional MRI (fMRI) during a working memory task was used to prospectively assess the pattern of brain activation and deactivation prior to and 1month after chemotherapy in BC patients who experienced CIA (n = 9), post-menopausal BC patients undergoing chemotherapy (n = 9), and pre- and post-menopausal healthy controls (n = 6 each). Neurocognitive testing was also performed at both time points. Repeated measures general linear models were used to assess statistical significance, and age was a covariate in all analyses. We observed a group-by-time interaction in the combined magnitudes of brain activation and deactivation (p = 0.006): the CIA group increased in magnitude from baseline to post-treatment while other groups maintained similar levels over time. Further, the change in brain activity magnitude in CIA was strongly correlated with change in processing speed neurocognitive testing score (r = 0.837 p = 0.005), suggesting this increase in brain activity reflects effective cognitive compensation. Our results demonstrate prospectively that the pattern of change in brain activity from pre- to post-chemotherapy varies according to pre-treatment menopausal status. Cognitive correlates add to the potential clinical significance of these findings. These findings have implications for risk appraisal and development of prevention or treatment strategies for cognitive changes in CIA.

Chemotherapy-induced amenorrhea in patients with breast cancer: basic mechanisms and diagnostic criteria of ovarian dysfunction

Occurrence of amenorrhea during chemotherapy in patients with breast cancer, some authors regard as a method of drug suppression of ovarian function. Chemotherapy-induced amenorrhea, due to the toxic effect of chemotherapy on the ovaries. Its appearance depends on the age of the patient, and the duration of chemotherapy protocol, as well as the cumulative dose of chemotherapy. Chemotherapy-induced amenorrhea occurs in 70% of premenopausal women, 40% of patients with breast cancer before age 40 years and 90% of women over 40. Several clinical trials show that the occurrence of amenorrhea during chemotherapy in patients with hormone-dependent breast cancer before age 50 improves survival. However, the absence of menstruation due to chemotherapy is not always an indication of adequate suppression of hormone-producing function of the ovaries and / or the onset of menopause. In this revue the main physiological mechanisms of chemotherapy-induced amenorrhea, as well as criteria for the diagnosis and clinical significance of various disorders of ovarian-menstrual cycle in premenopausal patients with breast cancer are discussed.

Impact of chemotherapy-induced amenorrhea in breast cancer patients: the evaluation of ovarian function by menstrual history and hormonal levels.

BackgroundChemotherapy-induced amenorrhea (CIA) is one of the most frequent therapy-related adverse events observed in breast cancer patients who have undergone chemotherapy. Although the characteristics of CIA have been studied in Western countries, little is known about CIA in Asian. We conducted a retrospective analysis to assess the characteristics and influencing factors of CIA and its association with menopause in Chinese women who underwent adjuvant chemotherapy for early-stage breast cancer.MethodsSeventy-three premenopausal women who underwent adjuvant chemotherapy for early stage (stages I to III) breast cancer were analyzed. Patient clinical characteristics, treatment regimes, menstrual information, and serum hormone values were collected retrospectively. Characteristic factors relevant to the onset of CIA and menopause were also estimated.ResultsApproximately 83.6% of patients developed CIA. Older patients (>40 years old) had higher CIA incidence compared with younger patients (P <0.0001). The onset of menopause was correlated with age (P <0.0001) and tamoxifen use (P = 0.0313). On the basis of the Kaplan–Meier analysis, a significant difference was observed in the time of onset of permanent amenorrhea as determined by menstrual history and hormone levels (P = 0.0028). In women aged 46 to 49 years, the beginning of permanent amenorrhea was detected earlier via the clinical method than via the hormonal method (2 months versus 23 months, P <0.0001). In the analysis of patients ≥50 years old, the median time to detection of permanent amenorrhea was 19 months in the hormonal test and 2 months in the clinical test (P = 0.0112).ConclusionsAge at diagnosis is a predictor of the onset of amenorrhea and transformation into menopause among premenopausal breast cancer patients. Adjuvant tamoxifen therapy substantially affects the onset of menopause. A delay of the onset of serum hormone postmenopausal status was observed compared with clinical symptoms. This interval was approximately 21 months in patients aged 46 to 49 years and 17 months in patients aged over 50 years. This interval is significant in the clinical estimate of the menstrual status.

Incidence and predictors of ovarian function recovery (OFR) in breast cancer (BC) patients with chemotherapy-induced amenorrhea (CIA) who switched from tamoxifen to exemestane

Aromatase inhibitors (AIs) may promote ovarian function recovery (OFR). True incidence, predictors and impact on the outcome of OFR are unknown. We carried out a prospective study to assess ovarian function in estrogen receptor (ER)-positive BC patients on tamoxifen who had at least 2 years of chemotherapy-induced amenorrhea (CIA) and postmenopausal E2 levels. Patients switched to exemestane and underwent a series of investigations including vaginal ultrasound, antimullerian hormone, follicle stimulating hormone (FSH), and E2. E2 measurements were made using a clinical assay (direct) and a highly sensitive (indirect) immunoassay for comparison. Both E2 assays (indirect versus direct) showed a similar incidence of OFR 32% (95% CI 19.5-44.5) versus 30% (95% CI 17.7-42.3) and median time to OFR 5.4 months (95% CI 1.2-9.6) versus 6.0 months (95% CI 4.8-7.1).On multivariate analysis, the mean age at the start of exemestane treatment was the only marker associated with probability of OFR (OR: 0.44, 0.24-0.78; P = 0.006). According to a receiver operating characteristic (ROC) analysis, age <48 years predicted for OFR (sensitivity: 59%; 1-specificity: 17%; AUC: 0.796; P = 0.001). Patients with OFR had higher mean E2 levels (43.6 versus 5.76 pmol/l; P = 0.001) and a reduced disease-free survival [DFS; HR 9.3 (95% CI 3.3-48.0; P = 0.04)] than those without it. Even with a clinical and biochemical profile compatible with menopause, switching from tamoxifen to an AI should be avoided in patients <48 with CIA.

Gonadatrophin Suppression to Prevent Chemotherapy-Induced Ovarian Damage

To estimate the effectiveness of gonadotropin-releasing hormone (GnRH) analogues cotreatment in preventing chemotherapy-induced amenorrhea in young breast cancer patients undergoing cyclophosphamide-based chemotherapy. One hundred hormone-insensitive breast cancer participants (aged 18-40 years) were recruited from two university-affiliated oncology centers in Egypt. Opting for type of cotreatment was based on available timeframe until start of chemotherapy. Fifty women ready for early chemotherapy were randomized to receive either chemotherapy alone (arm I) or chemotherapy after downregulation (estradiol less than 50 pg/mL) by GnRH antagonist and agonist (arm II). Then, GnRH antagonist was discontinued and agonist was continued until the end of chemotherapy. When chemotherapy was to start later than 10 days after study inclusion, 50 women were randomized to receive either chemotherapy alone (arm III) or chemotherapy after downregulation with GnRH agonist (arm IV). Resumption of menstruation at 12 months after end of chemotherapy was the primary outcome. Postchemotherapy hormonal and ultrasound changes were secondary outcomes. Twelve months after termination of chemotherapy, there were no differences in menstruation resumption rates between GnRH-treated patients and control group individuals in either early (80% in arms I and II, risk ratio 1, 95% confidence interval 0.7-.32; P=1.00) or delayed chemotherapy groups (80% and 84% in arms III and IV, risk ratio 0.95, 95% confidence interval 0.73-1.235; P=.71). There were no differences in hormonal and ultrasound markers between GnRH analogue users and control group individuals. The use of GnRH analogue cotreatment did not predict independently the odds of menstruating at 12 months. GnRH analogue cotreatment does not offer a significant protective effect on ovarian function in patients treated by cyclophosphamide-based chemotherapy. Australian New Zealand Clinical Trials Registry. www.anzctr.org.au, ACTRN12609001059257. I.

Goserelin with chemotherapy to preserve ovarian function in pre-menopausal women with early breast cancer: menstruation and pregnancy outcomes

Premature ovarian failure and infertility following chemotherapy in early breast cancer (EBC) are major concerns for young women. The role of gonadotrophin-releasing hormone (GnRH) agonists with chemotherapy in EBC in reducing the incidence of chemotherapy-induced early menopause remains uncertain, and long-term data on the recovery of fertility are sparse. We report an audit of our experience with the GnRH agonist, goserelin (Zoladex®), used with chemotherapy to preserve ovarian function and maintain fertility. Pre-menopausal women were given goserelin subcutaneously every 28 days during chemotherapy, starting 0-14 days before treatment. The main clinical end point was recovery of menstruation after chemotherapy. The other end points were rate of successful conception and median time to recovery of menses. About 84% of 125 women recovered menstruation with the median time to recovery of 6 months (1-43 months), including 76% of 71 patients aged over 35. Of the 42 patients who attempted pregnancy, 71% (n=30) managed to achieve pregnancies. At the time of analysis, there were 42 pregnancies and 30 healthy deliveries. The GnRH agonist, goserelin, given with chemotherapy for EBC is associated with a low risk of long-term chemotherapy-induced amenorrhoea and a high chance of pregnancy. Further randomised trials are needed.

Chemotherapy-Induced Amenorrhea – An Update

Chemotherapy-Induced Amenorrhea – An Update

Chemotherapy-Induced Amenorrhea - An Update.

Because of the heterogeneity in the definition of chemotherapy-induced amenorrhea (CIA) there are distinct differences in the literature with regard to its incidence as well as its dependence on various influencing factors. The occurrence of CIA varies greatly depending on the applied chemotherapy. The pathogenesis of CIA is especially based on a reduction of ovarian reserves. Various sonographic and biochemical factors can be used to exclude or confirm CIA. This is particularly important when an endocrine therapy with tamoxifen is not possible and the use of aromatase inhibitors is under consideration. CIA and especially the frequently thereby resulting early menopause can lead to pronounced restrictions in the quality of life of the affected patients, not least due to the resulting infertility. On the other hand, various studies have shown that CIA may have a positive prognostic significance. Thus, the identification of measures to prevent CIA (for example, through the use of GnRH analogues) is of particular importance.

Resumption or persistence of menstruation after cytotoxic chemotherapy is a prognostic factor for poor disease-free survival in premenopausal patients with early breast cancer

We investigated the relationship between resumption or persistence of menstruation after cytotoxic chemotherapy (RM) and disease-free survival (DFS) in premenopausal patients with early breast cancer. Medical records from 872 patients who received cytotoxic chemotherapy for stage I to III breast cancer were retrospectively reviewed. The median patient age was 41 years (range, 21-54) and the median follow-up duration was 6.2 years (range, 0.7-10.4). Six hundred ninety-two patients (79.4%) were hormone receptor (HR) positive and the majority of these received tamoxifen therapy after completing chemotherapy. The chemotherapy-induced amenorrhea (CIA) rate was 76.7% (n = 669), and 51.8% (n = 452) experienced RM during the follow-up period. One hundred twenty-one (13.9%) patients had persistent menstruation without CIA. DFS was significantly affected by younger age at diagnosis (≤35 years) (P = 0.013), tumor size > 2 cm (P < 0.001), node positivity (P < 0.001), HR negativity (P < 0.001), HER2 positivity (P = 0.010), and RM (P < 0.001). HR negativity [hazard ratio 1.7, 95% confidence interval (CI) 1.2-2.4, P = 0.006], tumor size > 2 cm (hazard ratio 2.1, 95% CI 1.4-3.0, P < 0.001), node positivity (hazard ratio 3.0, 95% CI 2.0-4.7, P < 0.001), and RM (hazard ratio 1.8, 95% CI 1.2-2.7, P = 0.004) remained significant factors for DFS on multivariate analysis. A considerable proportion of premenopausal patients treated with chemotherapy experienced RM after CIA. RM was a poor prognostic factor for DFS in premenopausal patients with early breast cancer.

Chemotherapy-induced amenorrhea in premenopausal breast cancer patients treated with adjuvant anthracycline and taxane based chemotherapy within the SUCCESS study.

554 Background: Chemotherapy induced amenorrhea (CIA) is often used as a surrogate marker for cytotoxic gonadal damage. The aim of this analysis was to identify predicitve factors for CIA in premenopausal breast cancer patients treated with adjuvant chemotherapy. Methods: The German multicenter, phase III SUCCESS trial compared 3 cycles of FEC q3w followed by 3x docetaxel q3w vs. FEC followed by Doc+gemcitabine as adjuvant treatment in patients with node positive or high risk node negative primary breast cancer. Premenopausal patients with hormone receptor positive tumors underwent endocrine treatment with tamoxifen (Tam) for 5 years. Additional goserelin (GnRH) for 2 years was given in the following cases: Age &lt;40 years at study entry, premenopausal hormone status or regular menses within 6 months after chemotherapy. We retrospectively investigated CIA rates of 1.189 initially premenopausal patients during disease-free follow-up. Results: Median age at diagnosis was 44 years (range 21-50). The median follow up time was 44 months (range 1-62). 791 patients (66.5%) received endocrine treatment. Tam intake was reported in 370 patients, GnRH in 29 patients, Tam+GnRH in 392 patients. In 963 patients (81.0%) CIA occurred for ≥3 months after chemotherapy. In 22.7% of initially amenorrheic patients CIA was temporary. 192 patients (16.2%) had continuous menstrual bleeding. In multivariate analysis the risk of CIA was significantly higher in older patients, increasing by factor 1.32 per life year (p&lt;0.0001). Tam intake was also associated with increased CIA rates (p=0.0032). Patients with combined Tam+GnRH were more likely to resume menses compared to patients without endocrine therapy (p=0.0056). Factors like the cytotoxic regimen, tumor stage, grading, the patient`s BMI or the use of GnRH analogues as ovarian protectants during chemotherapy did not correlate with CIA rates. Conclusions: Age was the strongest predictor for CIA. Tam administered alone increased CIA rates. Opposite effects were observed for patients who received Tam+GnRH. The addition of gemcitabine to sequential anthracyline-taxane based chemotherapy did not influence CIA.