The relative value of anti-Müllerian hormone to predict premature menopause in patients receiving adjuvant chemotherapy for breast cancer: Results from the OPTION trial.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1094-1094 ◽  
Author(s):  
Robert C. F. Leonard ◽  
Douglas Adamson ◽  
Gianfilippo Bertelli ◽  
Michelle McLinden ◽  
Nan Haiying ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Multivariate Logistic Regression Analysis ◽  
Premenopausal Women ◽  
Menstrual Bleeding ◽  
Premature Menopause ◽  
Ovarian Activity ◽  
Ovarian Protection ◽  
Pre Treatment

1094 Background: The OPTION trial in premenopausal women tested the ovarian protection effect of goserelin (G) given randomly before and during adjuvant chemotherapy for breast cancer. Methods: Using standard chemotherapy, women were randomised in 2 strata, under 40 yrs and over 40 yrs at diagnosis. 227 patients were recruited by end December 2009. 173 met the criteria for 1 year follow-up for this analysis; 140 patients of these had provided adequate data on menstrual bleeding; 87 patients were aged under 40 and 53 patients were aged over 40 at the time of chemotherapy. Cessation of menstruation during chemotherapy was defined as at least two consecutive cycles with no menstrual bleeding since the previous cycle and no return of menstrual bleeding prior to the final cycle of chemotherapy. Of those patients who had ceased periods during chemotherapy, those with no further menstrual bleeding at 12 months follow up were deemed to be menopausal. Patients were randomised to receive G or no G at start of chemotherapy. Primary endpoint was recovery of menses at 12 months from start of chemotherapy. AMH was measured in 117 women pre-treatment, and at 1 year after starting chemotherapy. Results: There were no differences in pretreatment AMH between control and goserelin-treated groups, thus further analyses were performed on all women grouped together. AMH was lower following chemotherapy (0.40±0.65 vs 1.38±1.82ng/ml; mean±SD; P<0.001)). Pre-treatment AMH was a significant predictor of post-treatment amenorrhoea (P=0.001). By multivariate logistic regression analysis with age and AMH, age remained significant (P=0.003) whereas AMH did not (P=0.07). Grouping pre-treatment and post-chemo AMH into quartiles showed that AMH became undetectable in 94% of women with lowest pre-treatment AMH vs 46.2% of women with the highest pretreatment AMH. We have previously demonstrated in a small cohort that pretreatment AMH can predict long-term (5 year) ovarian activity in women with breast cancer. Conclusions: The present data confirm the value of pretreatment AMH in assessing the likelihood of ongoing ovarian activity after chemotherapy for early breast cancer.

Evidence of a castration-mediated effect of adjuvant cytotoxic chemotherapy in premenopausal breast cancer.

1987 ◽  
Vol 5 (11) ◽  
pp. 1771-1778 ◽  
Author(s):  
H Brincker ◽  
C Rose ◽  
F Rank ◽  
H T Mouridsen ◽  
A Jakobsen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Premenopausal Women ◽  
Cytotoxic Chemotherapy ◽  
Axillary Node ◽  
Similar Degree ◽  
Premenopausal Breast Cancer ◽  
Free Survival ◽  
Adjuvant Trial

This prospective randomized trial, conducted by the Danish Breast Cancer Cooperative Group, is the largest study, so far, of adjuvant chemotherapy in premenopausal breast cancer. The trial is unique in that it is nationwide and based on a nonselected population of patients, and is the only adjuvant trial studying the effect of cyclophosphamide monotherapy. After total mastectomy with axillary node sampling, followed by local radiotherapy, 1,032 pre- and perimenopausal women with operable breast cancer were randomized to observation alone, or to adjuvant chemotherapy for 1 year with either cyclophosphamide monotherapy or with a combination of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF). As of January 1987, median follow-up was 68 months. From early on both cyclophosphamide alone and CMF were found to improve recurrence-free survival (RFS) significantly and to a similar degree (P = .0001). However, an overall survival advantage did not become evident until 5 years after the start of treatment. So far, this advantage appears to be more pronounced in CMF (P = .0065) than in cyclophosphamide-only patients (P = .08). Thus, the study confirms the findings of the National Surgical Adjuvant Breast Project (NSABP) and Milan trials that adjuvant chemotherapy prolongs the survival of premenopausal women with early breast cancer. A retrospective analysis revealed that, in contrast with CMF, cyclophosphamide alone did not improve RFS significantly in subsets of patients without amenorrhea, with estrogen-receptor (ER) negative tumors, and with tumors of low histological differentiation. Assuming that cyclophosphamide alone is a less tumoricidal treatment than CMF, these findings suggest that the effect of adjuvant cytotoxic chemotherapy is mediated partly through chemical castration, and partly through a purely cytotoxic effect.

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

1996 ◽  
Vol 14 (5) ◽  
pp. 1718-1729 ◽  
Author(s):  
J Bines ◽  
D M Oleske ◽  
M A Cobleigh
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Breast Cancer Survivors ◽  
Ovarian Function ◽  
Menopausal Status ◽  
Premenopausal Women ◽  
Premature Menopause ◽  
Premenopausal Breast Cancer ◽  
Wide Range ◽  
Definition Of

PURPOSE 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. DESIGN 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. RESULTS 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. CONCLUSION 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.

Incidence, Time Course, and Determinants of Menstrual Bleeding After Breast Cancer Treatment: A Prospective Study

2006 ◽  
Vol 24 (7) ◽  
pp. 1045-1051 ◽  
Author(s):  
Jeanne A. Petrek ◽  
Michelle J. Naughton ◽  
L. Douglas Case ◽  
Electra D. Paskett ◽  
Elizabeth Z. Naftalis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Treatment ◽  
Repeated Measures ◽  
Time Course ◽  
Ovarian Function ◽  
Premenopausal Women ◽  
Recovery Phase ◽  
Breast Cancer Treatment ◽  
Menstrual Bleeding

Purpose To assess ovarian function using the surrogate of monthly bleeding after breast cancer treatment in premenopausal women. Patients and Methods Five hundred ninety-five US women age 20 to 45 years were accrued from January 1998 to July 2002 within 8 months of diagnosis with stages I to III breast cancer (median follow-up 45 months). Daily bleeding records were obtained prospectively, as well as extensive clinical, demographic, quality of life, and treatment data. Repeated measures logistic regression was used to assess which variables were predictive of monthly bleeding. Results Significantly different proportions of women had monthly bleeding depending on their age (P < .001), chemotherapy program (P < .001), and time since treatment regimen. In the month after the standard course of doxorubicin and cyclophosphamide (AC), whether or not followed by paclitaxel or docetaxel, approximately 16% had monthly bleeding compared with the cyclophosphamide, methotrexate, fluorouracil (CMF) group, in which 48% bled (P < .001). Following any AC regimen, there was a slow recovery phase of about 9 months followed by a plateau, during which almost half continued monthly bleeding for the remainder of the follow-up period compared with after CMF in which there was no recovery phase and a continual decline in monthly bleeding to approximately 18% of women at study end (P < .001). Tamoxifen use decreased bleeding between months 12 and 24 after chemotherapy with 15% fewer women having bleeding. Conclusion Using daily menstrual bleeding records, it is demonstrated that age, the specific chemotherapy regimen received, and tamoxifen use impact ovarian function.

Randomized Trial Comparing Cyclophosphamide, Epirubicin, and Fluorouracil With Cyclophosphamide, Methotrexate, and Fluorouracil in Premenopausal Women With Node-Positive Breast Cancer: Update of National Cancer Institute of Canada Clinical Trials Group Trial MA5

2005 ◽  
Vol 23 (22) ◽  
pp. 5166-5170 ◽  
Author(s):  
Mark N. Levine ◽  
Kathleen I. Pritchard ◽  
Vivien H.C. Bramwell ◽  
Lois E. Shepherd ◽  
Dongsheng Tu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Early Stage ◽  
Premenopausal Women ◽  
Axillary Node ◽  
Group V ◽  
Node Positive ◽  
Original Report ◽  
Positive Breast Cancer

Purpose Certain anthracycline-containing adjuvant chemotherapy regimens are associated with improved relapse-free survival (RFS) and overall survival (OS) compared with the classic regimen of cyclophosphamide, methotrexate, and fluorouracil in women with early-stage breast cancer. Patients and Methods Between 1989 and 1993, 710 pre- and perimenopausal women with axillary node–positive breast cancer were randomly assigned to either cyclophosphamide 75 mg/m2 orally days 1 through 14, epirubicin 60 mg/m2 intravenously days 1 and 8, and fluorouracil 500 mg/m2 intravenously days 1 and 8 (CEF) or CMF (cyclophosphamide 100 mg/m2 orally days 1 through 14, methotrexate 40 mg/m2 intravenously days 1 and 8, and fluorouracil 600 mg/m2 intravenously days 1 and 8). On the basis of follow-up to May 1997 (median follow-up time, 59 months), there was a statistically significant improvement in RFS and OS for CEF compared with CMF. Results The trial results are now updated, with a median follow-up of 10 years for live patients. The 10-year RFS is 52% for patients who received CEF compared with 45% for CMF patients (hazard ratio [HR] for CMF v CEF = 1.31; stratified log-rank, P = .007). The 10-year OS for patients who received CEF and CMF are 62% and 58%, respectively (HR for CMF v CEF = 1.18; stratified log-rank, P = .085). The rates of acute leukemia have not changed since the original report, whereas the rates of congestive heart failure are slightly higher but acceptable (four patients [1.1%] in the CEF group v one patient [0.3%] in the CMF group). Conclusion The previously demonstrated benefit of CEF compared with CMF adjuvant chemotherapy is maintained with longer follow-up in the MA5 trial.

scholarly journals Staging Investigations in Asymptomatic Early Breast Cancer Patients at the Cancer Centre of Southeastern Ontario

2021 ◽  
Vol 28 (3) ◽  
pp. 2190-2198
Author(s):  
Dalia Kamel ◽  
Veronica Youssef ◽  
Wilma M. Hopman ◽  
Mihaela Mates
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Early Breast Cancer ◽  
Triple Negative ◽  
Metastatic Breast ◽  
Receptor Status ◽  
Cancer Centre ◽  
Radiological Staging

Background: In 2012, the American Society for Clinical Oncology (ASCO) identified five key opportunities in oncology to improve patient care, recommending against imaging tests for the staging of patients with early breast cancer (EBC) at low risk for metastases. Similarly, the European Society of Medical Oncology (ESMO) guideline does not support radiological staging in asymptomatic EBC (aEBC). The purpose of this study was to assess local practice and outcomes of staging investigations (SIs) in aEBC at the Cancer Centre of Southeastern Ontario (CCSEO). Methods: A retrospective electronic and paper chart review was undertaken to identify all aEBC patients treated at our institution between January 2012 and December 2014. Patients with pathological staging of T1-T2 and N0-1 with any receptor status were included. We collected patient demographics, treatment and pathologic tumor characteristics. The use and outcomes of initial and follow-up SIs were recorded. Data were analyzed to determine associations between the use of SIs and clinical characteristics (chi-square tests, independent samples t-tests and Mann–Whitney U tests). Results: From 2012 to 2014, 295 asymptomatic EBC patients were identified. The mean age was 64, 81% were postmenopausal and 76% had breast conserving surgery. Stage distribution was as follows: stage I 42%, stage IIA 37% and stage IIB 21%. Receptor status was as follows: ER+ 84%, HER2+ 13% and triple negative 12%. Adjuvant chemotherapy was received by 36%, Trastuzumab by 10% and endocrine therapy by 76% of patients. Baseline SIs were performed in 168 patients (57%) for a total of 332 tests. Overt metastatic disease was found in five patients (one bone scan and four CT scans). Seventy-one out of the 168 patients (42%) who received initial staging imaging underwent 138 follow-up imaging tests, none of which were diagnostic for metastases. Nine patients with suspicious CT findings underwent biopsies, of which four were malignant (one metastatic breast cancer and three new primaries). Factors significantly associated with SI were as follows: younger age (p = 0.001), premenopausal status (p = 0.01), T2 stage (p < 0.001), N1 stage (p < 0.001), HER2 positive (p < 0.001), triple negative status (p = 0.007) and use of adjuvant chemotherapy (p < 0.001). Conclusions: Over a 3-year period at our institution, more than 50% of aEBC patients underwent a total of 470 initial and follow-up staging tests, yielding a cancer diagnosis (metastatic breast cancer or second primary cancer) in four patients. We, therefore, conclude that routine-staging investigations in aEBC patients have low diagnostic value, supporting current guidelines that recommend against the routine use of SI in this population.

scholarly journals Sequential Versus Concurrent Trastuzumab in Adjuvant Chemotherapy for Breast Cancer

2011 ◽  
Vol 29 (34) ◽  
pp. 4491-4497 ◽  
Author(s):  
Edith A. Perez ◽  
Vera J. Suman ◽  
Nancy E. Davidson ◽  
Julie R. Gralow ◽  
Peter A. Kaufman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Growth Factor Receptor ◽  
Disease Free Survival ◽  
Standard Of Care ◽  
Phase Iii ◽  
P Value ◽  
Sequential Administration ◽  
Taxane Chemotherapy

Purpose NCCTG (North Central Cancer Treatment Group) N9831 is the only randomized phase III trial evaluating trastuzumab added sequentially or used concurrently with chemotherapy in resected stages I to III invasive human epidermal growth factor receptor 2–positive breast cancer. Patients and Methods Patients received doxorubicin and cyclophosphamide every 3 weeks for four cycles, followed by paclitaxel weekly for 12 weeks (arm A), paclitaxel plus sequential trastuzumab weekly for 52 weeks (arm B), or paclitaxel plus concurrent trastuzumab for 12 weeks followed by trastuzumab for 40 weeks (arm C). The primary end point was disease-free survival (DFS). Results Comparison of arm A (n = 1,087) and arm B (n = 1,097), with 6-year median follow-up and 390 events, revealed 5-year DFS rates of 71.8% and 80.1%, respectively. DFS was significantly increased with trastuzumab added sequentially to paclitaxel (log-rank P < .001; arm B/arm A hazard ratio [HR], 0.69; 95% CI, 0.57 to 0.85). Comparison of arm B (n = 954) and arm C (n = 949), with 6-year median follow-up and 313 events, revealed 5-year DFS rates of 80.1% and 84.4%, respectively. There was an increase in DFS with concurrent trastuzumab and paclitaxel relative to sequential administration (arm C/arm B HR, 0.77; 99.9% CI, 0.53 to 1.11), but the P value (.02) did not cross the prespecified O'Brien-Fleming boundary (.00116) for the interim analysis. Conclusion DFS was significantly improved with 52 weeks of trastuzumab added to adjuvant chemotherapy. On the basis of a positive risk-benefit ratio, we recommend that trastuzumab be incorporated into a concurrent regimen with taxane chemotherapy as an important standard-of-care treatment alternative to a sequential regimen.

scholarly journals Goserelin for Ovarian Protection during Breast-Cancer Adjuvant Chemotherapy

2015 ◽  
Vol 372 (10) ◽  
pp. 923-932 ◽  
Author(s):  
Halle C.F. Moore ◽  
Joseph M. Unger ◽  
Kelly-Anne Phillips ◽  
Frances Boyle ◽  
Erika Hitre ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Ovarian Protection
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