NCIC CTG MA.17: Tolerability of letrozole among ethnic minority women

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6018-6018
Author(s):  
B. Moy ◽  
D. Tu ◽  
L. E. Shepherd ◽  
J. L. Pater ◽  
T. J. Whelan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ethnic Minority ◽  
Early Stage ◽  
Bodily Pain ◽  
Disease Free Survival ◽  
Minority Women ◽  
Wilcoxon Test ◽  
Future Research ◽  
Change Scores ◽  
Sf 36

6018 Background: Disease free survival was significantly improved in women receiving letrozole after standard adjuvant tamoxifen in the MA.17 trial. Based on the results of MA.17 and of other trials of aromatase inhibitors in early stage breast cancer, chronic aromatase inhibitor therapy, in postmenopausal women free of breast cancer recurrence, is now being widely employed. We analyzed the toxicity of letrozole according to ethnic status among women enrolled in MA.17. Methods: The chi-square test was used for comparison of rates of side effects between the two groups, Caucasian vs. ethnic minority (defined as all non-Caucasians). In a subset of women, quality of life (QOL) was assessed by the SF-36 Health Survey. Mean change scores in QOL from baseline were compared between groups for summary measures and domains using the Wilcoxon test. Results: 352 minority women and 4,708 Caucasians were enrolled in MA.17, of which 183 minority women and 2,339 Caucasians were randomized to receive letrozole. Caucasians were older than minority women and had a slightly longer duration of treatment with prior tamoxifen. Tumor size and nodal status were not significantly different between the two groups. In women who received letrozole, minority women had significantly lower incidence of hot flashes (49% vs. 58%; p = 0.02), fatigue (29% vs. 39%; p = 0.005), and arthritis (2% vs. 7%; p = 0.006) compared with Caucasians. Mean QOL change scores of SF-36 domains for women who received letrozole were not different but minority women had better mental health at 6 month assessment (p = 0.02) and worse bodily pain at 12 month assessment (p = 0.046). Conclusions: Minority women tolerated letrozole considerably better than Caucasians in the MA.17 trial. These preliminary findings suggest that minority women respond differently to letrozole in terms of toxicity. Recent demonstration of genotypic variations in the aromatase gene in different ethnic groups plus likely pharmacogenomic differences suggests that further research is needed to clarify the clinical outcomes of aromatase inhibition in women of diverse ethnicities. Future research strategies should focus on examining in vivo genotype-phenotype correlations to determine the effects of genetic variation on response to anticancer therapy and on toxicities and end-organ effects. [Table: see text]

Patient-reported outcomes from MA.17R: A randomized trial of extending adjuvant letrozole for 5 years after completing an initial 5 years of aromatase inhibitor therapy alone or preceded by tamoxifen in postmenopausal women with early-stage breast cancer.

2016 ◽  
Vol 34 (18_suppl) ◽  
pp. LBA506-LBA506 ◽  
Author(s):  
Julie Lemieux ◽  
Paul E. Goss ◽  
Wendy R. Parulekar ◽  
James N. Ingle ◽  
Kathleen I. Pritchard ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Aromatase Inhibitor ◽  
Sexual Functioning ◽  
Disease Free Survival ◽  
Wilcoxon Test ◽  
Phase Iii ◽  
Vasomotor Symptoms ◽  
Change Scores ◽  
Sf 36 ◽  
Patient Reported

LBA506 Background: MA.17R is a Canadian Cancer Trials Group (CCTG) led phase III randomized controlled trial comparing letrozole to placebo after 5 years of aromatase inhibitor (AI) as adjuvant therapy for hormone-receptor positive breast cancer. The primary endpoint was disease-free survival. Quality of life (QOL) was a secondary endpoint. Methods: QOL was measured with the SF-36 (2 summary scores and 8 domains) and menopause-specific QOL (MENQOL) (4 symptom domains) at baseline and every 12 months (mo) up to 60 mo. QOL assessment was mandatory for CCTG centres but optional to centres in other groups. Mean change scores from baseline were calculated at 12 and 36 mo. Between-arm differences were assessed with the Wilcoxon test. Results: 1918 patients were randomized and 1428 patients completed the baseline QOL assessment. Compliance with QOL measures was over 85%. Baseline summary scores for SF-36 physical (PCS, 47.5 for letrozole and 47.9 for placebo) and mental (MCS, 55.5 for letrozole and 54.8 for placebo) were close to population norms (50). No differences were seen between groups in mean change scores for the SF-36 PCS and MCS and the other 8 QOL domains. Patients randomized to letrozole reported worse vasomotor symptoms (12 mo p = 0.02, 36 mo p = 0.03) and worse sexual functioning (12 mo p = 0.01, 36 mo p = 0.01). Further analyses with follow up to 60 months will be presented. Conclusions: No differences were seen in overall QOL measured by the SF 36 summary measures between letrozole and placebo groups. Differences existed for vasomotor symptoms and sexual functioning which were worse in the letrozole group and attributed to improvements in mean scores seen for women randomized to placebo. The data indicate that continuation of AI therapy after 5 years prior treatment is not associated with a deterioration of overall QOL. Treatment related vasomotor and sexual functioning alterations occur with ongoing treatment. Clinical trial information: NCT00754845.

NCIC CTG MAP.3: Symptoms and quality of life (QoL) among racial/ethnic minority women taking the aromatase inhibitor (AI) exemestane (EXE) for breast cancer risk reduction.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6557-6557
Author(s):  
Beverly Moy ◽  
Dongsheng Tu ◽  
Harriet Richardson ◽  
Elizabeth Maunsell ◽  
Paul E. Goss
Keyword(s):  
Mental Health ◽  
Aromatase Inhibitor ◽  
Ethnic Minority ◽  
Hot Flashes ◽  
Bodily Pain ◽  
Minority Women ◽  
Vaginal Dryness ◽  
Sf 36 ◽  
Significant Difference ◽  
Racial Ethnic

6557 Background: Racial/ethnic minority postmenopausal women reported fewer side effects than whites on the aromatase inhibitor (AI) letrozole in MA.17. We present symptoms and QoL according to race and ethnicity in women taking EXE for BC prevention in MAP.3. Methods: Adjusted proportions ever experiencing symptoms or reporting worsened SF-36 domains (change scores from baseline decreased by ≥ -5 points) among racial minorities (M) and whites (W), and Hispanics (H) and non-Hispanics (non-H), were compared using logistic regression models adjusting for age, body mass index (BMI), country, marital status, education level and employment status. Results: Of 2285 women randomized to EXE, 2231 (97.6%) women had race information: 129 M (6.1%) and 2102 W (93.9%).Compared to W, M were significantly older, had higher BMI, had lower Gail scores, received more drugs for cardiovascular diseases, and were more likely to live in the United States.M women experienced fewer sweats (12% vs. 22%; p = 0.005) and less vaginal dryness (8% vs. 16%; p=0.03). No significant difference between W and M was seen in the proportion with worsened QoL on any SF-36 domain. Ethnicity was known for 2198 women on EXE (96.2%): 241 H (11.0%) and 1957 non-H (89%). The following were less frequent among H women: hot flashes (21% vs. 42%; p<0.0001); fatigue (14% vs. 24%; p=0.01); sweats (5% vs. 24%; p<0.0001); insomnia (6% vs. 11%; p=0.001); heartburn (5% vs. 16%; p=0.001); nausea (3% vs. 7%; p=0.02); arthritis (5% vs. 12%; p=0.02); depression (7% vs. 11%; p=0.005); back pain (2% vs. 10%; p=0.002); cough (4% vs. 11%; p=0.02); and vaginal dryness (4% vs. 17%; p<0.0001). Fewer H women reported worsening in SF-36 bodily pain (60 vs. 66%; p=0.02) but more reported worsening in SF-36 mental health (59% vs. 48%; p=0.02). Conclusions: Consistent with MA.17 findings, racial/ethnic minorities experienced fewer adverse events on AI. H women had less bodily pain but reported worsening mental health. These differences may be important for minority women contemplating EXE for BC prevention. Genotypic variations and pharmocogenomics that might account for these differences merit investigation.

scholarly journals The role of functional polymorphisms in oxidative stress-related genes on early-stage breast cancer survival

2021 ◽  
pp. 172460082110111
Author(s):  
Erika Korobeinikova ◽  
Rasa Ugenskiene ◽  
Ruta Insodaite ◽  
Viktoras Rudzianskas ◽  
Jurgita Gudaitiene ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Single Nucleotide Polymorphisms ◽  
Early Stage ◽  
Disease Free Survival ◽  
Early Stage Breast Cancer ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Free Survival ◽  
Disease Free

Background: Genetic variations in oxidative stress-related genes may alter the coded protein level and impact the pathogenesis of breast cancer. Methods: The current study investigated the associations of functional single nucleotide polymorphisms in the NFE2L2, HMOX1, P21, TXNRD2, and ATF3 genes with the early-stage breast cancer clinicopathological characteristics and disease-free survival, metastasis-free survival, and overall survival. A total of 202 Eastern European (Lithuanian) women with primary I–II stage breast cancer were involved. Genotyping of the single nucleotide polymorphisms was performed using TaqMan single nucleotide polymorphisms genotyping assays. Results: The CA+AA genotypes of P21 rs1801270 were significantly less frequent in patients with lymph node metastasis and larger tumor size ( P=0.041 and P=0.022, respectively). The TT genotype in ATF3 rs3125289 had significantly lower risk of estrogen receptor (ER), progesterone receptor (PR) negative, and human epidermal growth factor receptor 2 (HER2) positive status ( P=0.023, P=0.046, and P=0.040, respectively). In both, univariate and multivariate Cox analysis, TXNRD2 rs1139793 GG genotype vs. GA+AA was a negative prognostic factor for disease-free survival (multivariate hazard ratio (HR) 2.248; P=0.025) and overall survival (multivariate HR 2.248; P=0.029). The ATF3 rs11119982 CC genotype in the genotype model was a negative prognostic factor for disease-free survival (multivariate HR 5.878; P=0.006), metastasis-free survival (multivariate HR 4.759; P=0.018), and overall survival (multivariate HR 3.280; P=0.048). Conclusion: Our findings suggest that P21 rs1801270 is associated with lymph node metastasis and larger tumor size, and ATF3 rs3125289 is associated with ER, PR, and HER2 status. Two potential, novel, early-stage breast cancer survival biomarkers, TXNRD2 rs1139793 and ATF3 rs11119982, were detected. Further investigations are needed to confirm the results of the current study.

Advances in Adjuvant Endocrine Therapy for Postmenopausal Women

2008 ◽  
Vol 26 (5) ◽  
pp. 798-805 ◽  
Author(s):  
Nancy U. Lin ◽  
Eric P. Winer
Keyword(s):  
Breast Cancer ◽  
Postmenopausal Women ◽  
Endocrine Therapy ◽  
Hormone Receptor ◽  
Disease Free Survival ◽  
Breast Cancer Diagnosis ◽  
Endocrine Treatment ◽  
Future Research ◽  
Sequential Approach ◽  
Hormone Receptor Positive

Hormone receptor-positive cancers are the most common tumor subtype among postmenopausal women with breast cancer. Despite substantial improvements in disease-free survival and overall survival with tamoxifen and chemotherapy, recurrences still occur, and may ultimately lead to death from breast cancer. Importantly, disease recurrence includes both early and late events, with over half of all recurrences detected more than 5 years from initial breast cancer diagnosis. In recent years, a number of large, randomized trials have evaluated the role of the aromatase inhibitors (AIs) in postmenopausal women with hormone receptor-positive breast cancer. These studies have tested one of three approaches: (1) an upfront AI, (2) a sequential approach after 2-3 years of tamoxifen, and (3) extended endocrine therapy beyond 5 years. Results of these studies have challenged the previous standard of a 5-year course of tamoxifen alone. While the AIs have become a standard component of treatment for most postmenopausal women, many questions remain as to how best tailor endocrine treatment to individual patients. In addition, despite the gains achieved with the AIs, many recurrences are not prevented, and novel strategies are urgently needed, particularly for those women at high risk of recurrence. In this article, we review the efficacy and toxicity data from the available trials of endocrine therapy in the postmenopausal setting. We outline controversies in choosing the optimal endocrine approach, and we discuss selected ongoing studies. Finally, we highlight future research directions, such as the need to understand host and tumor heterogeneity.

scholarly journals Assessing the Clinical Benefit of Systemic Adjuvant Therapies for Early Breast Cancer

2017 ◽  
Vol 77 (10) ◽  
pp. 1079-1087 ◽  
Author(s):  
Volker Möbus ◽  
Susanne Hell ◽  
Marcus Schmidt
Keyword(s):  
Breast Cancer ◽  
Early Breast Cancer ◽  
Clinical Benefit ◽  
Early Stage ◽  
Survival Rates ◽  
Disease Free Survival ◽  
New Drugs ◽  
Early Stage Breast Cancer ◽  
Risk Of Recurrence ◽  
Adjuvant Therapies

AbstractOncologic therapy is currently undergoing significant changes. A number of innovative targeted medications currently in clinical development have raised high expectations. With that in mind, discussions about terms such as “clinical benefit” and “clinical relevance” are highly topical. This also applies to further developments in the field of adjuvant systemic therapies for early-stage breast cancer. As the treatment aim is curative, assessment of the clinical benefit of adjuvant therapies must be largely based on efficacy outcomes. The focus must be on improving disease-free survival rates and lowering the risk of recurrence. Because of the current low mortality rates, statements about overall survival rates are only possible after very long observation periods. Consequently, new drugs in adjuvant therapies should be considered as offering a clinical benefit, if they reduce the risk of recurrence below current low levels of risk. The evidence for established adjuvant therapy standards in early-stage breast cancer can be used as objective criteria for comparison. This review article considers the requirements for clinical benefit of new adjuvant therapies for early breast cancer, based on examples from adjuvant endocrine therapy, adjuvant polychemotherapy and adjuvant anti-HER2 therapy.

Cholesterol, Cholesterol-Lowering Medication Use, and Breast Cancer Outcome in the BIG 1-98 Study

2017 ◽  
Vol 35 (11) ◽  
pp. 1179-1188 ◽  
Author(s):  
Signe Borgquist ◽  
Anita Giobbie-Hurder ◽  
Thomas P. Ahern ◽  
Judy E. Garber ◽  
Marco Colleoni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Early Stage ◽  
Cancer Recurrence ◽  
Disease Free Survival ◽  
Distant Recurrence ◽  
Cholesterol Lowering ◽  
Hormone Receptor Positive ◽  
Cholesterol Levels ◽  
Free Interval

Purpose Cholesterol-lowering medication (CLM) has been reported to have a role in preventing breast cancer recurrence. CLM may attenuate signaling through the estrogen receptor by reducing levels of the estrogenic cholesterol metabolite 27-hydroxycholesterol. The impact of endocrine treatment on cholesterol levels and hypercholesterolemia per se may counteract the intended effect of aromatase inhibitors. Patients and Methods The Breast International Group (BIG) conducted a randomized, phase III, double-blind trial, BIG 1-98, which enrolled 8,010 postmenopausal women with early-stage, hormone receptor–positive invasive breast cancer from 1998 to 2003. Systemic levels of total cholesterol and use of CLM were measured at study entry and every 6 months up to 5.5 years. Cumulative incidence functions were used to describe the initiation of CLM in the presence of competing risks. Marginal structural Cox proportional hazards modeling investigated the relationships between initiation of CLM during endocrine therapy and outcome. Three time-to-event end points were considered: disease-free-survival, breast cancer–free interval, and distant recurrence–free interval. Results Cholesterol levels were reduced during tamoxifen therapy. Of 789 patients who initiated CLM during endocrine therapy, the majority came from the letrozole monotherapy arm (n = 318), followed by sequential tamoxifen-letrozole (n = 189), letrozole-tamoxifen (n = 176), and tamoxifen monotherapy (n = 106). Initiation of CLM during endocrine therapy was related to improved disease-free-survival (hazard ratio [HR], 0.79; 95% CI, 0.66 to 0.95; P = .01), breast cancer–free interval (HR, 0.76; 95% CI, 0.60 to 0.97; P = .02), and distant recurrence–free interval (HR, 0.74; 95% CI, 0.56 to 0.97; P = .03). Conclusion Cholesterol-lowering medication during adjuvant endocrine therapy may have a role in preventing breast cancer recurrence in hormone receptor–positive early-stage breast cancer. We recommend that these observational results be addressed in prospective randomized trials.

Outcomes after Surgery for Early Stage Breast Cancer in Women Staged With Preoperative Breast Magnetic Resonance Imaging According to Breast Tissue Density

2019 ◽  
Vol 1 (2) ◽  
pp. 115-121
Author(s):  
Renata Faermann ◽  
Jonathan Weidenfeld ◽  
Leonid Chepelev ◽  
Wayne Kendal ◽  
Raman Verma ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Tissue ◽  
Early Stage ◽  
Disease Free Survival ◽  
Breast Mri ◽  
Early Stage Breast Cancer ◽  
Free Survival ◽  
Tissue Density ◽  
Breast Tissue Density ◽  
Preoperative Breast Mri

Abstract Purpose To determine surgical outcomes and breast cancer disease-free survival outcomes of women with early stage breast cancer with and without use of preoperative breast MRI according to breast tissue density. Methods Women with early stage breast cancer diagnosed from 2004 to 2009 were classified into 2 groups: 1) those with dense and heterogeneously dense breasts (DB); 2) those with nondense breasts (NDB) (scattered fibroglandular and fatty replaced tissue). The 2 groups were reviewed to determine who underwent preoperative MRI. Breast tissue density was determined with mammography according to ACR BI-RADS. Patients were compared according to tumor size, grade, stage, and treatment. Survival analysis was performed using Kaplan-Meier estimates. Results In total, 261 patients with mean follow-up of 85 months (25–133) were included: 156 DB and 105 NDB. Disease-free survival outcomes were better in the DB group in patients with MRI than in those without MRI: patients with MRI had significantly fewer local recurrences (P &lt; 0.016) and metachronous contralateral breast cancers (P &lt; 0.001), but this was not the case in the NDB group. Mastectomies were higher in the DB group with preoperative MRI than in those without MRI (P &lt; 0.01), as it was in the NDB group (P &gt; 0.05). Conclusions Preoperative breast MRI was associated with reduced local recurrence and metachronous contralateral cancers in the DB group, but not in the NDB group; however, the DB patients with MRI had higher mastectomy rates.

Sign in / Sign up

Export Citation Format

Share Document