Incidence Of Chemotherapy-induced Amenorrhea Research Articles

Age as an Independent Factor in the Permanent Chemotherapy-Induced Amenorrhea Incidence in Breast Cancer Patients at Dr. Moewardi Hospital, Surakarta, Indonesia

Background: Chemotherapy Induced Amenorrhea (CIA) is one common side effect of chemotherapy in breast cancer patients. Some who have CIA may experience menstruation return while others experience permanent CIA.
 Aim: to examines the factors that contribute to the incidence of persistent CIA in breast cancer patients.
 Methods: The population of this retrospective study was new breast cancer patients with premenopausal status when they started receiving chemotherapy at dr Moewardi Hospital Surakarta, Indonesia, from January 2019 to July 2021. To determine the relationship, the chi-square/Fisher’s exact test was performed. Risk factor analysis on the incidence of permanent CIA was carried out by using a bivariate logistic regression test, followed by multivariate analysis.
 Results: A number of 105 premenopausal breast cancer patients who received chemotherapy were found. Of these patients, 97 (93.38%) patients experienced CIA and 8 patients (6.62%) continued to menstruate. Of all the subjects having CIA, 49 patients (46.67%) menstruated again while the other 48 (45.71%) had persistent CIA. Age factor has a significant relationship with the incidence of permanent CIA (p =< 0.001), where patients aged > 45 years tend to have permanent CIA incidence with a proportion of 42 patients (87.5%) (p < 0.05). The multivariate analysis showed that age > 45 years (OR = 75.117; 95% CI = 12.671-445.311; p = < 0.001) was the most dominant risk factor associated with the incidence of permanent CIA, while other variables as risk factors for permanent CIA based on multivariate analysis were Stage III (R = 6.677; 95% CI = 1.370-32,545; p = 0.019) compared to stages I and II, and BMI in the normal category (OR = 5.485; 95% CI = 1.083-27.786; p = 0.040) compared to excess BMI. The other variables were not found to be associated with the incidence of permanent CIA.
 Conclusion: Age is a major factor associated with permanent CIA incidence. Other factors related to this study are staging and BMI.
 
 Keywords: Age, Permanent, Chemotherapy Induced Amenorrhea, Breast Cancer

Chemotherapy-induced amenorrhea and its effects on fertility in long-term female survivors of classic osteosarcoma.

To explore the effect of chemotherapy-induced amenorrhea (CIA) on female osteosarcoma patients' fertility function, we investigated and analyzed their marital status, fertility, and menstrual status in a retrospective cohort study. We selected female osteosarcoma patients from database from January 2004 to December 2013. Patients' characteristics such as age, tumor location, marital status, menstrual status, and fertility status were collected. The data were analyzed using the Statistical Package for the Social Sciences (SPSS), version 22. A total of 122 female patients met these criteria and finally responded by questionnaire and telephone follow-up. The marriage rate of female osteosarcoma survivors was 50.8% (62/122), which was significantly lower than the control group (p = 0.000). The average marriage age of female osteosarcoma survivors was 25.5, which was obviously higher than the control group (p = 0.000). CIA occurred in 46 (36.1%) patients. We then found that the incidence of CIA was higher in older patients. (p = 0.011). All of the married patients wanted to have children, and 67.8% (42/62) of them had given birth after chemotherapy. The fertility of married patients with CIA was significantly reduced compared to that of married patients without CIA. (p = 0.001). The patients with CIA have higher risk of impaired reproductive function than those who did not. Fertility preservation option before the start of the chemotherapy is important. And it is much value to record menstrual pattern and detect sex steroid levels after 6months of therapy in order to be able to evaluate the fertility status.

L’insuffisance ovarienne chimio-induite dans le cancer du sein : étude rétrospective de 100 cas

Breast cancers affect about a quarter of women of reproductive age worldwide. Chemotherapy is frequently indicated due to the aggressive biomolecular cancer subtypes usually observed in the localized forms, which may compromise the fertility of these young patients. The aim of our study is to report the incidence of chemotherapy induced ovarian failure in premenopausal breast cancer patients after chemotherapy, and to identify related risk factors. It is a retrospective cross-sectional cohort study which included all premenopausal patients with early breast cancer treated at the department of medical oncology, Hassan II University Hospital of Fez, during a period of one year. Chemotherapy induced amenorrhea (CIA) and associated risk factors were studied. The study included 100 patients. The mean age of the subjects was 36 years. The incidence of CIA was 82%, 66.7% regained menstruations. Risk factors associated with CIA were analyzed, only the patient age at diagnosis was found to be statistically significantly associated with CIA. Our study found a high incidence of CIOF (Chemotherapy-induced ovarian failure) with a relatively low incidence of reversible amenorrhea. Only the patient age has been shown to be an independent factor, statistically significantly associated with ovarian failure after chemotherapy. Methods of fertility preservation should be considered in those patients to reduce the impact of chemotherapy on ovarian reserves.

NSAS-BC02 substudy of chemotherapy-induced amenorrhea (CIA) in premenopausal patients who received either taxane alone or doxorubicin(A) cyclophosphamide(C) followed by taxane as postoperative chemotherapy

Chemotherapy-induced amenorrhea (CIA) is one of the critical side effects from the chemotherapy in premenopausal patients with breast cancer. The goals of our study are the following: (1) to investigate the factors affecting the incidence of CIA; and (2) to evaluate the prognostic role of CIA in premenopausal patients with breast cancer. We conducted a post hoc retrospective substudy to examine the incidence of the CIA and the relationship between CIA and prognosis in NSAS-BC02 that compared taxane alone to Doxorubicin(A) Cyclophosphamide(C) followed by taxane in postoperative patients with node-positive breast cancer RESULTS: Of 395 premenopausal women, 287 (72.7%) had CIA due to protocol treatment. Regarding type of protocol regimen, proportion of CIA was 76.9% in AC Paclitaxel(P), 75.2% in AC Docetaxel(D), 62.8% in PTX, and 75.2% in DTX. Predictive factors of CIA were age increase by 5years (OR 1.50), ER positivity (OR 2.08), and HER2 3 + ( OR 0.40) according to logistic regression analysis. According to the log rank test and the Cox proportional hazards model, CIA group had significantly better disease-free survival than non-CIA group (P < .0001). However, according to time-dependent Cox model that was used to reduce guarantee-time bias, CIA was not a statistically significant prognostic factor in both ER-positive and ER-negative patients. Treatment with taxane alone caused high frequency of CIA in premenopausal women with breast cancer. CIA did not turn out to be an independent prognostic factor, taking guarantee-time bias into consideration. Further clinical studies are needed to validate these findings.

Chemotherapy-induced amenorrhea and the resumption of menstruation in premenopausal women with hormone receptor-positive early breast cancer.

For premenopausal women with breast cancer, information on the effects of chemotherapy and the risk of infertility is important. In this study, the effect of chemotherapy on the ovarian function in premenopausal women with hormone receptor-positive breast cancer was investigated, with an age-stratified analysis of the appearance of amenorrhea and the resumption of menstruation after the use of chemotherapy with anthracyclines or taxanes. Premenopausal women diagnosed with operable Stage I-III hormone receptor-positive breast cancer and underwent neoadjuvant or adjuvant chemotherapy with the standard regimen of anthracyclines and/or taxanes were included. The patients were classified into age groups in 5-year increments, and the rates of chemotherapy-induced amenorrhea (CIA), resumption of menstruation, and duration of CIA after chemotherapy were analyzed. The subjects consisted of 101 patients (median age 45years). CIA occurred in 97 (96%) patients and 40 patients resumed menstruation. In all patients aged ≤39years menstruation restarted, whereas in all patients aged ≥50years, menstruation did not restart. For the patients who resumed menstruation, the younger the patients, the sooner menstruation tended to restart. The resumption of menstruation occurred within 1year for younger patients aged around 30years, but for those aged ≥35years, 60% of cases took around 2-3years for resumption. The incidence of CIA, the resumption of menstruation and duration of CIA after chemotherapy depend greatly on the patient's age.

Chemotherapy-Induced Amenorrhea and Menopause Symptoms in Women With Breast Cancer

Chemotherapy is a common adjuvant therapy for breast cancer that improves survival rates by killing residual cancer cells. However, this intervention may damage the germ cells within the ovary and interrupt the menstrual cycle, ultimately leading to chemotherapy-induced amenorrhea (CIA). The incidence of CIA depends on how broadly this term is defined. Around 75% of premenopausal breast cancer women treated with chemotherapy will develop CIA. Age, having a relatively long chemotherapy cycle duration, being estrogen-receptor positive, and using Tamoxifen all increase the risk of CIA. Although CIA may be associated with better prognosis outcomes, breast cancer women must subsequently deal with the various menopausal symptoms that are associated with a CIA-induced drop in estrogen level (such as cognitive function decline, physical and psychological symptoms, vasomotor symptoms, reproductive and sexual function problems, and body weight change). The present article describes the female menstrual cycle, the mechanism and risk factors of CIA, and the range of menopausal symptoms. Furthermore, we summarized methods of assessing menopausal symptoms and compared five common rating scales of menopausal symptoms. By better understanding the potential menopausal symptoms, researchers and clinicians may then select the most appropriate scale based on the situational needs in order to evaluate the severity of menopausal symptoms that are experienced by breast cancer women.

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.

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.

Incidence of reversible amenorrhea in women with breast cancer undergoing adjuvant anthracycline and taxen-based chemotherapy.

e11025 Background: To determine the incidence of reversible amenorrhea in women with breast cancer undergoing adjuvant anthracycline and taxane-based chemotherapy. Methods: We studied the incidence and duration of amenorrhea induced by adjuvant chemotherapy(regimens: 6EC(Epirubicin and cyclophosphamide) or 4EC follow by 4Taxen) in 68 premenopausal patients with different age group. Reversible amenorrhea was defined as recovery of regular menses or premenopausal hormone values (luteinizing hormone (LH), follicle-stimulating hormone (FSH) and estradiol) in the year following the end of chemotherapy. Results: The incidence of chemotherapy-induced amenorrhea(CIA) at the end of chemotherapy was similar in the two groups: 81.3% in the 6EC arm and 86.3% in the 4EC/4T arm. The incidence of CIA was not significance higher in the middle age arm(older than 40 years old) than in the younger arm(40 or younger than 40 years old): 97.4% versus 86.7% (P=0.114). However, more reversible amenorrhea was observed in younger arm than in middle age arm (76.7% vs. 34.2%, P=0.001). The median duration of regular menses recovering was 9 months in the younger arm and 11 months in the median age arm. More persistent amenorrhea had been detected in the middle age arm than in younger arm: 63.2% vs.10%, P&lt;0.001). Multivariate analysis showed that age (&gt;40years) was independently associated with the incidences of CIA (P=0.048). Conclusions: Age was the strongest predictor of the incidence of amenorrhea during adjuvant chemotherapy. Our study suggests that most of CIA in younger patients induced by adjuvant chemotherapy were reversible amenorrhea. Therefore adjuvant aromatase inhibitors for early breast cancer patients with CIA should be cautiously administered.

Incidence of chemotherapy-induced amenorrhea in premenopausal women treated with adjuvant FOLFOX for colorectal cancer.

e14112 Background: The gonadotoxicity of oxaliplatin-based chemotherapy is largely unknown. Studies indicate that the incidence of young women diagnosed with colorectal cancer is rising, thus there is an increasing number of female colorectal cancer (crc) survivors of premenopausal and child-bearing age. Adjuvant FOLFOX chemotherapy is the most widely used standard treatment for stage III and high-risk stage II colon cancer. The objective of this analysis was to evaluate the incidence of FOLFOX induced amenorrhea in women age 50 or younger treated with adjuvant therapy for colorectal cancer. Methods: A search of computerized 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. Results: Seventy three patients returned the questionnaire. Twenty four patients were excluded from analysis; 19 were treated with radiotherapy, 1 patient had undergone bilateral oophorectomy, 1 had a hysterectomy and 3 stopped menstruating prior to diagnosis. Forty nine patients were analyzed. In total, 41% experienced amenorrhea during chemotherapy. Sixteen percent had persistent amenorrhea approximately one year after completion of chemotherapy. The incidence of amenorrhea during chemotherapy and persistent amenorrhea was higher in patients age 40 or older than in patients under 40 (59% vs 31% (p=.17) and 24% vs 13% (p=.33), respectively). Conclusions: In this retrospective study, it appears that the incidence of FOLFOX chemotherapy induced amenorrhea is increased with age. Due to the small sample size the study may be underpowered to detect a statistical difference. Prospective studies are planned to more accurately characterize the impact of FOLFOX on early menopause and fertility.

The Risk of Amenorrhea Is Related to Chemotherapy-Induced Leucopenia in Breast Cancer Patients Receiving Epirubicin and Taxane Based Chemotherapy

BackgroundChemotherapy-induced amenorrhea (CIA) is common in young breast cancer patients. The incidence of CIA associated with regimens involving epirubicin and taxane was not well known. Furthermore, previous studies suggested leucopenia and amenorrhea may reflect inter-individual variations in pharmacokinetics. The purpose of this study was to investigate the association between leucopenia after first cycle of chemotherapy and CIA in young breast cancer patients receiving epirubicin and taxane based chemotherapy. Furthermore, the incidence of CIA was also assessed.Methodology and Principal FindingsBetween October 2008 and March 2010, 186 consecutive premenopausal patients, treated with epirubicin and taxane based chemotherapy, were recruited. Information about CIA was collected by telephone and out-patient clinic. Of these 186 patients, data from 165 patients were included and analyzed. Of all 165 patients, CIA occurred in 72 patients (43.64%). In multivariate analysis, age older than 40 y (OR: 16.10, 95% CI: 6.34–40.88, P<0.001) and previous childbearing (OR: 3.17, 95% CI: 1.06–9.47, P = 0.038) were significantly associated with probability of CIA. Compared to patients treated without taxane, patients treated with taxane-contained regimens did not have a significantly higher rate of CIA (P>0.05). The rate of CIA in leucopenia group (52.56%) was significantly higher than that in normal leukocyte group (34.62%) (P = 0.024). In patients treated with a FEC regimen (cyclophosphamide, epirubicin and 5-fluorouracil), the rate of CIA in leucopenia group (59.57%) was significantly higher than that in normal leukocyte group (36.84%) (P = 0.037).ConclusionsAge at diagnosis and previous childbearing were both found to significantly increase the risk of CIA, whereas additional taxane was not associated with increased rate of CIA. Importantly, leucopenia after first cycle of chemotherapy was associated with increased risk of CIA, which suggested that leucopenia may be an early predictor of chemotherapy-induced infertility.

P3-14-19: Impact of Chemotherapy-Induced Amenorrhea on Response to Neoadjuvant Chemotherapy in Breast Cancer.

Abstract BACKGROUND: Although chemotherapy and ovarian ablation independently improve the outcome of breast cancer, there is controversy about the benefit of chemotherapy-induced amenorrhea (CIA) in breast cancer. We investigated impact of CIA on response to neoadjuvant chemotherapy in breast cancer patients. METHODS: We reviewed the records of 198 premenopausal patients with breast cancer treated with neoadjuvant chemotherapy between January 2005 and December 2010. Chemotherapy-induced amenorrhea (CIA) was defined as serum FSH level ≥40 IU/L after completion of all scheduled neoadjuvant chemotherapy and prior to definitive surgery. RESULTS: Among 198 breast cancer patients, 132 pts (66.7%) developed CIA after neoadjuvant chemotherapy. 156 pts (78%) underwent DA chemotherapy. The age of CIA patients was older than non-CIA patients (41.55±5.55 years vs. 38.27 ± 6.86 years, p=0.001). The incidence of CIA after neoadjuvant chemotherapy was significantly higher in responder group (responder vs. nonresponder: 87 pts (74.4%) vs. 45 pts (55.6%); p=0.006). Additionally, FSH level after all scheduled neoadjuvant chemotherapy was significantly higher in responder group (FSH 56.41±32.41 IU/L vs. 45.76±30.31 IU/L; p=0.021). In univariate analysis, CIA (p=0.006) and total number of chemotherapy cycle regardless of chemotherapy regimen (p=0.04) were significantly associated with tumor response. CIA was only independent factor for tumor response after neoadjuvant chemotherapy on multivariate analysis (p=0.012). CONCLUSION: CIA after neoadjuvant chemotherapy was significantly associated with response to neoadjuvant chemotherapy in locally advanced breast cancer. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-14-19.

Chemotherapy-induced amennorrhea: Predictive markers of response to neoadjuvant chemotherapy in breast cancer.

281 Background: There is controversy about the benefit of chemotherapy-induced amenorrhea (CIA) in breast cancer. We investigated significance of CIA after neoadjuvant chemotherapy for predicting response to neoadjuvant chemotherapy in breast cancer patients. Methods: We reviewed the records of 198 premenopausal patients with breast cancer treated with neoadjuvant chemotherapy between January 2005 and December 2010. Chemotherapy-induced amenorrhea (CIA) was defined as serum FSH level ≥40 IU/L after completion of all scheduled neoadjuvant chemotherapy and prior to definitive surgery. Results: Among 198 breast cancer patients, 132 pts (66.7%) developed CIA after neoadjuvant chemotherapy. 156 pts (78%) underwent DA chemotherapy. The age of CIA patients was older than non-CIA patients (41.55±5.55 vs. 38.27± 6.86 years, p=0.001). The incidence of CIA after neoadjuvant chemotherapy was significantly higher in responder group (responder vs. nonresponder: 87 pts (74.4%) vs. 45 pts (55.6%); p=0.006). Additionally, FSH level after all scheduled neoadjuvant chemotherapy was significantly higher in responder group (FSH 56.41±32.41 mIU/ml vs. 45.76±30.31 mIU/ml; p=0.021). In univariate analysis, CIA (p=0.006) and total number of chemotherapy cycle regardless of chemotherapy regimen (p=0.04) were significantly predictive of tumor response. CIA was only significant predictive factor for tumor response after neoadjuvant chemotherapy on multivariate analysis (p=0.012). Conclusions: CIA is independent predictive markers of response to neoadjuvant chemotherapy in locally advanced breast cancer.

Switching to aromatase inhibitor (AI) after tamoxifen in premenopausal patients with chemotherapy-induced amenorrhea (CIA) after early breast cancer treatment.

e11099 Background: AI are contraindicated in women with functioning ovaries as the reduced feedback of estrogen leads to an increased secretion of gonadotropins. Previous data obtained in our center confirms that the incidence of CIA among premenopausal patients is 75.5% - 82.7% depending on the chemotherapy administered. The aim of our study was to analyze outcome in terms of ovarian function recovery in premenopausal patients treated with tamoxifen that switched to AI after long-term CIA (>1 year) and/or estradiol levels < 20 pmol. Methods: 102 patients diagnosed with hormone-sensitive early breast cancer at the Hospital Clinico of Valencia, and clinically premenopausal at diagnosis were included from May 2004 to December 2009. All patients were treated with chemotherapy in the adjuvant or neoadjuvant setting, and adjuvant tamoxifen. Patients had to accomplish criteria of postmenopausal status at the time of switching defined as a period of CIA of more than 1 year and/or levels of estradiol < 20 pmol/L. Results: Median age at switching was 49.8 years, 81 patients were 45 years or older, 19 patients were 40-44 years and 2 treated with high-dose chemotherapy were younger than 40 years. 40% received both anthracyclines and taxanes and 14% high-dose adjuvant chemotherapy. 87 patients were switched after at least 2 years of tamoxifen, and to 15 patients switching was offered earlier due to tamoxifen intolerance. Monitoring of estradiol levels was obtained in 55 patients (53.9%) at the time of switch, of whom 46 presented levels of estradiol < 20 pmol/L. In 9 patients (7.8%) ovarian function returned with renewal of menses and serum estradiol levels > 20 pmol/L. None of the patients younger than 40 returned to normal ovarian function. Conclusions: AI should be used with caution in premenopausal patients after CIA. However, with an appropriate monitoring and follow-up, incidence of recovery of ovarian function occured in only 7.8% of the patients. Switch to an AI in patients younger than 40 with CIA after high dose CT may be a safe procedure.

Incidence of chemotherapy-induced amenorrhea in premenopausal patients with breast cancer following adjuvant anthracycline and taxane

The purpose of this study was to determine the incidence of amenorrhea among breast cancer patients aged 40years and younger following adjuvant chemotherapy. A follow-up questionnaire survey was conducted with premenopausal women with breast cancer who were treated with adjuvant anthracycline and taxane-based chemotherapy. In total, 66 women were retrospectively reviewed. Forty-nine patients were treated with a regimen containing anthracycline followed by taxane and 17 patients with anthracycline alone. Fifty-eight patients (87.9%) experienced amenorrhea during chemotherapy; 14 patients (21.2%) had persistent amenorrhea after chemotherapy. The incidence of amenorrhea during chemotherapy and persistent amenorrhea was higher in patients older than 36 than in younger patients (97.9 vs. 63.2%, 27.7 vs. 5.3%). Additional taxane resulted in a higher incidence of amenorrhea compared with anthracycline-containing regimen alone (93.9 vs. 70.6%). Multivariate analysis showed that age (≥36years) was independently associated with the incidences of amenorrhea during chemotherapy (p=0.007). Age was the strongest predictor of the incidence of amenorrhea during chemotherapy. It is unclear whether additional taxane may contribute to amenorrhea. This information could be useful in deciding whether to use adjuvant chemotherapy.

The Clinical Outcome of Chemotherapy-Induced Amenorrhea in Premenopausal Young Patients with Breast Cancer with Long-Term Follow-up

We investigated the factors that predict chemotherapy-induced amenorrhea (CIA) and the prognostic significance of CIA after long-term follow-up. We reviewed data from 241 premenopausal patients with breast cancer who underwent adjuvant CMF or FAC chemotherapy after breast cancer surgery between January 1995 and December 2000. The median follow-up duration was 109.8 (range, 16.6-193.1) months. The age of CIA patients was older than non-CIA patients (median, 44 (range, 28-53) years and 36 (range, 25-49) years, respectively; P < 0.001). The addition of tamoxifen to the chemotherapy increased the incidence of CIA from 48% to 63.6% (P = 0.015). The 10-year disease-free survival (DFS) rate was higher in the CIA group compared with the non-CIA group in hormonal receptor-positive patients (78.4% vs. 67%, respectively; P = 0.022), and the 10-year overall survival (OS) rate also was higher in the CIA group compared with the non-CIA group (90.8% vs. 79.7%, respectively; P = 0.041). The most important predictors of CIA are age and the addition of tamoxifen to the chemotherapy. CIA is likely to have an influence on DFS and OS in premenopausal patients with breast cancer with a positive hormone receptor, and it might be used as a surrogate marker for effective chemotherapy in these young Asian patients.

Incidence and time course of bleeding after long‐term amenorrhea after breast cancer treatment

The incidence of chemotherapy-induced amenorrhea (CIA) and the time to subsequent menstrual bleeding in premenopausal breast cancer patients treated with current standard chemotherapy regimens was examined. Four hundred sixty-six women ages 20 to 45 years at the time of diagnosis of a stage I to III breast cancer were recruited between January 1998 and July 2002. Patients completed monthly bleeding calendars from the time of study recruitment. Updated medical history data were obtained at 6-month intervals. Most women received doxorubicin and cyclophosphamide (AC); doxorubicin, cyclophosphamide, and paclitaxel (ACT); or cyclophosphamide, methotrexate, and 5-fluorouracil (CMF). Approximately 41% of women experienced an initial 6 months of CIA, and an additional 29% had at least 1 year of CIA. Approximately half of the women with 6 months of CIA and 29% of those with 1 year of CIA resumed bleeding within the subsequent 3 years, usually in the year after their amenorrheic episode. Resumption of bleeding differed significantly by treatment regimen after 6 months of CIA (P = .002; 68% with AC, 57% with ACT, and 23% with CMF), but not after 1 year of CIA (P = .5). Of the 23% of women who experienced an initial 2-year period of CIA, 10% resumed bleeding within the ensuing 3 years after their amenorrheic episode, but none had regular menses. A considerable proportion of women treated with chemotherapy will experience periods of CIA, but many will resume bleeding. Newer treatment regimens such as ACT appear to have a higher resumption of bleeding compared with CMF. This finding may have implications for choice of anti-estrogen treatment and for future potential pregnancies/fertility.

Incidence of chemotherapy-induced amenorrhea in hormone-sensitive breast cancer patients: the impact of addition of taxanes to anthracycline-based regimens

Adjuvant chemotherapy prolongs survival in patients with breast cancer, but it also causes side effects such as ovarian-function suppression. The incidence of chemotherapy-induced amenorrhea (CIA) varies depending on the patients' age, dose and the type of chemotherapy that they receive. CIA produced by anthracycline-based regimens has been widely studied, but less is known about the incidence of CIA caused by the combined use of taxanes and anthracyclines. It has been suggested that tamoxifen might influence the maintenance of amenorrhea. However, most studies of CIA have explored series of patients with hormone-sensitive and hormone-resistant tumors, so data about CIA could be strongly influenced by endocrine adjuvant therapy. The aims of our study were to assess the incidence of CIA with the addition of taxanes to anthracyclines regimens in pre- or perimenopausal patients diagnosed with hormone-sensitive breast cancer and to determine predictive factors for CIA. A retrospective non-randomized study was conducted in the Hospital Clinico Universitario of Valencia, Spain. Three hundred and five premenopausal and perimenopausal patients were recruited between January 1998 and May 2005, 212 of whom had been treated with anthracycline-based regimens and 93 with a combination of anthracyclines and taxanes. Amenorrhea was permanent in 222 patients (93.7%) and menses returned in 6.3%. CIA was present in 75.5% of patients treated with anthracyclines and in 82.7% of patients treated with anthracyclines and taxanes. This difference did not reach statistical significance (p = 0.16). CIA appeared in 95% of patients older than 45 years, while the proportion of CIA decreased to 52% in patients younger than 40 years. This suggests age as an important predictive factor for CIA (p < 0.001). Although a slightly superior incidence of CIA in patients with hormone-sensitive tumors treated with combination regimens was observed, no statistically significant difference in incidence was found. Age was found to be the main predictive factor for CIA in both groups.

Determinants of recovery from amenorrhea in premenopausal breast cancer patients receiving adjuvant chemotherapy in the taxane era

Chemotherapy-induced amenorrhea occurs in about 20-70% of premenopausal breast cancer patients. Chemotherapy-induced amenorrhea can affect choice of hormonal therapy, fertility, and quality of life of breast cancer survivors. We retrospectively analyzed the incidence of amenorrhea after adjuvant chemotherapy and the subsequent recovery of the menses in 145 breast cancer patients. Age, smoking, alcohol consumption, body mass index, chemotherapy regimen, previous hormonal therapies, and previous childbearing were analyzed as potential predictive factors of ovarian function recovery. Median age was 42 years at the beginning of adjuvant chemotherapy with 30.3% of patients below 40 years of age. The majority (87.6%) of patients received anthracycline-based chemotherapy, 35.2% of patients received a cyclophosphamide-methotrexate-5-fluorouracil regimen and 42.8% received a taxane. The incidence of chemotherapy-induced amenorrhea was 80, and 35.3% of these patients resumed menses after a median of 8 months. In multivariate analysis, younger age (<40 years, P=0.01) and taxane-based chemotherapy (P=0.03) were associated with increased probability of recovery of menses after chemotherapy-induced amenorrhea. In contrast, cyclophosphamide-methotrexate-5-fluorouracil-based chemotherapy (P=0.07) and previous childbearing (P=0.04) were associated with an increased probability of permanent chemotherapy-induced amenorrhea. Recovery of menses after chemotherapy-induced amenorrhea occurs more probably in younger women, with no pregnancies and receiving taxanes.

The Incidence of Chemotherapy-induced Amenorrhea and Recovery in Young (&lt;45-year-old) Breast Cancer Patients

Purpose: Although adjuvant chemotherapy improves the survival of premenopausal breast cancer patients, it could induce the premature menopause. The objective of this study was to investigate the incidence and risk factors of chemotherapy-induced amenorrhea (CIA) and recovery for young ( 30 mIU/mL. Results: A total of 324 patients were included in this study. Of these patients, 261 patients (80.6%) developed amenorrhea just after the completion of chemotherapy. During follow-up, 77 patients (29.5%) resumed menstruation. Amenorrhea rates at 6, 12, 24, and 36 months after chemotherapy were 72.2%, 66.6%, 58.1%, and 55.5%. Women who recovered from amenorrhea were significantly younger than the women who did not recover (p<0.001). Patients treated with cyclophosphamide, methotrexate and 5-fluorouracil (CMF) less frequently recovered from amenorrhea than patients who were treated with anthracycline or taxane-based chemo- therapy (p<0.001). Conclusion: The age of the patient was the most important factor for the development of CIA. Patients treated with a CMF regimen and older patients showed poor recovery from CIA. These results could be helpful to make decisions about the treatment strategies for premenopausal young women.