Aromatase inhibitors and the risk of contralateral breast cancer in BRCA mutation carriers.

2015 ◽  
Vol 33 (28_suppl) ◽  
pp. 3-3 ◽  
Author(s):  
Maryam Nemati Shafaee ◽  
Angelica M. Gutierrez-Barrera ◽  
Heather Y. Lin ◽  
Banu Arun
Keyword(s):  
Breast Cancer ◽  
Contralateral Breast Cancer ◽  
Multivariate Analyses ◽  
Brca Mutation ◽  
Contralateral Breast ◽  
Categorical Variables ◽  
Continuous Variables ◽  
Chi Square ◽  
Estrogen Receptor Positive

3 Background: Contralateral breast cancer (CBC) risk in BRCA1 & 2 mutations is up to 64%. Patients (pts) with estrogen receptor positive (ER+) breast cancer (BC) are offered tamoxifen (TAM) or Aromase inhibitors (AI) adjuvantly. Reports suggest that TAM may reduce the risk of CBC in BRCA mutation; however there is no such data on the effect of AIs. Here, we evaluate the effect of TAM and AI as potential CBC risk reducers in a cohort of women with known BRCA status. Methods: 1043 BC pts receiving genetic counseling and BRCA testing were included. 13 had metastasis, 168 had a variant BRCA, and 50 had synchronous BC, and were excluded. Of the 812 remaining pts, 153 had a deleterious BRCA 1 or 2 mutations. Pts were followed from the diagnosis of BC until CBC, death, or last follow-up. The study had IRB approval. Univariate analyses were performed to test the significance of each variable in relation to BRCA status using chi-square tests for categorical variables and t tests for continuous variables. Results: The median age at diagnosis of BC was 42.3 years (range: 21-84). Median follow up was 8.6 years. 86% (700) had ER+ tumors, 80% were diagnosed with T1-2, and 81% had N0-N1. 76% (622) received TAM, and 37% (304) received AI. A total of 68 (8.7%) CBCs occurred of which 14% (21/153) occurred in BRCA carriers vs 7% (47/659) in BRCA non-carriers. Multivariate analyses indicated that BRCA status and AI use were significantly associated with CBC. Specifically, compared with BRCA negative, pts with BRCA1+ or BRCA2+ had larger hazard of developing CBC, Hazard Ratio (HR) (95% confidence interval (CI)) = 2.49 (1.21, 5.10), p = 0.013 for BRCA1+ vs Negative. HR (95%CI) = 1.97 (1.05, 3.73), p = 0.036 for BRCA2+ vs Negative. Compared to pts who did not receive AI, those who received AI had smaller hazard of developing CBC, HR (95%CI) = 0.42 (0.22, 0.81), p = 0.01. The interaction between AI and BRCA status was not significant (p = 0.4), hence all pts benefited from AI use in terms of CBC risk reduction. TAM use did not show significant effect on the risk of CBC in univariate and multivariate analyses (p > 0.13). Conclusions: This is the first report showing that AIs can reduce risk of CBC in women with BC who have a BRCA mutation. This finding should be validated in larger independent cohorts.

scholarly journals Germline BRCA Mutation and Clinical Outcomes in Breast Cancer Patients Focusing on Survival and Failure Patterns: A Long-Term Follow-Up Study of Koreans

Medicina ◽  
2020 ◽  
Vol 56 (10) ◽  
pp. 514
Author(s):  
Hakyoung Kim ◽  
Doo Ho Choi ◽  
Won Park
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Contralateral Breast Cancer ◽  
Brca Mutation ◽  
Contralateral Breast ◽  
Breast Cancer Patients ◽  
Mutation Status ◽  
Free Survival ◽  
Failure Patterns

Background and Objectives: This study aimed to evaluate the effect of a BRCA mutation on survival and failure patterns, focusing on the risk of ipsilateral recurrence and contralateral breast cancer in patients. Materials and Methods: We retrospectively reviewed medical records of 300 patients with breast cancer who underwent genetic screening for BRCA1/2 genes and were treated at Samsung Medical Center between 1 January 2000 and 31 December 2010. Ultimately, clinical outcomes of 273 patients were analyzed. Results: The median follow-up duration was 102 months (range, 1 to 220 months). Patients with BRCA1/2-mutated tumors had a shorter 10-year disease-free survival (DFS) rate compared to those with non-mutated tumors (62.8% vs. 80.0%, p = 0.02). Regarding failure patterns, patients with BRCA1/2-mutated tumors showed a higher incidence of contralateral breast cancer than those with non-mutated tumors (BRCA1/2 non-mutated vs. mutated tumors: 4.9% vs. 26.0%, p < 0.001). BRCA mutation status remained a significant prognostic factor for contralateral breast recurrence-free survival (HR: 4.155; 95% CI: 1.789–9.652; p = 0.001). Korean patients with a BRCA mutation showed inferior DFS compared to those without a BRCA mutation. Conclusions: BRCA mutation status is a strong predictor of recurrence in contralateral breast cancer. Strategies such as prophylactic treatment and active surveillance should be discussed with breast cancer patients who have a BRCA mutation.

scholarly journals Impact of Pre-Operative Breast Magnetic Resonance Imaging (MRI) on Contralateral Synchronous and Metachronous Breast Cancer Detection- A Case Control Comparison Study With Mean Follow-Up of 102 Months.

2021 ◽  
Author(s):  
Wen-Pei Wu ◽  
Chih-Yu Chen ◽  
Chih-Wei Lee ◽  
Hwa-Koon Wu ◽  
Shou-Tung Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Detection ◽  
Contralateral Breast Cancer ◽  
Breast Mri ◽  
Contralateral Breast ◽  
Conventional Imaging ◽  
Metachronous Breast Cancer ◽  
Group B ◽  
Synchronous Breast Cancer

Abstract Background: Women with unilateral breast cancer are at an increased risk for the development of contralateral breast cancers. We hypothesis that combined breast MRI would detect more contralateral synchronous breast cancer than conventional imaging alone, and resulted in less contralateral metachronous breast cancer during follow-up. Methods: In this case control analysis, we retrospectively collected two groups of patients for evaluating the effectiveness and value of adding pre-operative breast MRI to conventional breast images (mammography and sonography) for detection of contralateral synchronous breast cancer. The new metachronous contralateral breast cancer diagnosed during follow-up was prospectively evaluated and compared. Results: Group A (n=733) comprised patients who underwent conventional preoperative imaging and group B (n=735) combined with MRI were enrolled and compared. Seventy (9.5%) of the group B patients were found to have contralateral lesions detected by breast MRI, and 65.7% of these lesions only visible with MRI. The positive predictive value of breast MRI detected contralateral lesions was 48.8%. With the addition of breast MRI to conventional imaging studies, more surgical excisions were performed in contralateral breasts (6% (44/735) versus 1.4% (10/733), P< 0.01), more synchronous contralateral breast cancer detected (2.9% (21/735) versus 1.1% (8/733), P=0.02), and resulted in numerical less (2.2% (16/714) versus 3% (22/725), p=0.3) metachronous contralateral breast cancer during a mean follow-up of 102 months. Conclusions: Combining pre-operative breast MRI evaluation resulted in an increase of contralateral synchronous breast cancer detection, and a numerical less subsequent contralateral metachronous breast cancer occurrence compared to conventional imaging alone.

scholarly journals Risk of contralateral breast cancer according to first breast cancer characteristics among women in the USA, 1992–2016

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Cody Ramin ◽  
Diana R. Withrow ◽  
Brittny C. Davis Lynn ◽  
Gretchen L. Gierach ◽  
Amy Berrington de González
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Cumulative Incidence ◽  
Contralateral Breast Cancer ◽  
Breast Cancer Treatment ◽  
Contralateral Breast ◽  
Breast Cancer Patients ◽  
Younger Women ◽  
Er Positive

Abstract Background Estimates of contralateral breast cancer (CBC) risk in the modern treatment era by year of diagnosis and characteristics of the first breast cancer are needed to assess the impact of recent advances in breast cancer treatment and inform clinical decision making. Methods We examined CBC risk among 419,818 women (age 30–84 years) who were diagnosed with a first unilateral invasive breast cancer and survived ≥ 1 year in the US Surveillance, Epidemiology, and End Results program cancer registries from 1992 to 2015 (follow-up through 2016). CBC was defined as a second invasive breast cancer in the contralateral breast ≥ 12 months after the first breast cancer. We estimated standardized incidence ratios (SIRs) of CBC by year of diagnosis, age at diagnosis, and tumor characteristics for the first breast cancer. Cumulative incidence of CBC was calculated for women diagnosed with a first breast cancer in the recent treatment era (2004–2015, follow-up through 2016). Results Over a median follow-up of 8 years (range 1–25 years), 12,986 breast cancer patients developed CBC. Overall, breast cancer patients had approximately twice the risk of developing cancer in the contralateral breast when compared to that expected in the general population (SIR = 2.21, 95% CI = 2.17–2.25). SIRs for CBC declined by year of first diagnosis, irrespective of age at diagnosis and estrogen receptor (ER) status (p-trends < 0.001), but the strongest decline was after an ER-positive tumor. The 5-year cumulative incidence of CBC ranged from 1.01% (95% CI = 0.90–1.14%) in younger women (age < 50 years) with a first ER-positive tumor to 1.89% (95% CI = 1.61–2.21%) in younger women with a first ER-negative tumor. Conclusion Declines in CBC risk are consistent with continued advances in breast cancer treatment. The updated estimates of cumulative incidence inform breast cancer patients and clinicians on the risk of CBC and may help guide treatment decisions.

scholarly journals The Influence of Adjuvant Systemic Regimens on Contralateral Breast Cancer Risk and Receptor Subtype

2019 ◽  
Vol 111 (7) ◽  
pp. 709-718 ◽  
Author(s):  
Iris Kramer ◽  
Michael Schaapveld ◽  
Hester S A Oldenburg ◽  
Gabe S Sonke ◽  
Danielle McCool ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Reduction ◽  
Endocrine Therapy ◽  
Aromatase Inhibitors ◽  
Contralateral Breast Cancer ◽  
Contralateral Breast ◽  
Receptor Subtype ◽  
Therapy Regimen ◽  
Netherlands Cancer Registry

Abstract Background An increasing number of breast cancer (BC) survivors are at risk of developing contralateral breast cancer (CBC). We aimed to investigate the influence of various adjuvant systemic regimens on, subtype-specific, risk of CBC. Methods This population-based cohort study included female patients diagnosed with first invasive BC between 2003 and 2010; follow-up was complete until 2016. Clinico-pathological data were obtained from the Netherlands Cancer Registry and additional data on receptor status through linkage with PALGA: the Dutch Pathology Registry. Cumulative incidences (death and distant metastases as competing risk) and hazard ratios (HRs) were estimated for all invasive metachronous CBC and CBC subtypes. Results Of 83 144 BC patients, 2816 developed a CBC; the 10-year cumulative incidence was 3.8% (95% confidence interval [CI] = 3.7% to 4.0%). Overall, adjuvant chemotherapy (HR = 0.70, 95% CI = 0.62 to 0.80), endocrine therapy (HR = 0.46, 95% CI = 0.41 to 0.52), and trastuzumab with chemotherapy (HR = 0.57, 95% CI = 0.45 to 0.73) were strongly associated with a reduced CBC risk. Specifically, taxane-containing chemotherapy (HR = 0.48, 95% CI = 0.36 to 0.62) and aromatase inhibitors (HR = 0.32, 95% CI = 0.23 to 0.44) were associated with a large CBC risk reduction. More detailed analyses showed that endocrine therapy statistically significantly decreased the risk of estrogen receptor (ER)-positive CBC (HR = 0.41, 95% CI = 0.36 to 0.47) but not ER-negative CBC (HR = 1.32, 95% CI = 0.90 to 1.93) compared with no endocrine therapy. Patients receiving chemotherapy for ER-negative first BC had a higher risk of ER-negative CBC from 5 years of follow-up (HR = 2.84, 95% CI = 1.62 to 4.99) compared with patients not receiving chemotherapy for ER-negative first BC. Conclusion Endocrine therapy, chemotherapy, as well as trastuzumab with chemotherapy reduce CBC risk. However, each adjuvant therapy regimen had a different impact on the CBC subtype distribution. Taxane-containing chemotherapy and aromatase inhibitors were associated with the largest CBC risk reduction.

Long-Term Benefits of 5 Years of Tamoxifen: 10-Year Follow-Up of a Large Randomized Trial in Women at Least 50 Years of Age With Early Breast Cancer

2011 ◽  
Vol 29 (13) ◽  
pp. 1657-1663 ◽  
Author(s):  
Allan Hackshaw ◽  
Michael Roughton ◽  
Sharon Forsyth ◽  
Kathryn Monson ◽  
Krystyna Reczko ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Breast Cancer ◽  
Contralateral Breast Cancer ◽  
Disease Free Survival ◽  
Contralateral Breast ◽  
Free Survival ◽  
Free Data ◽  
Cv Disease

Purpose The Cancer Research UK “Over 50s” trial compared 5 and 2 years of tamoxifen in women with early breast cancer. Results are reported after median follow-up of 10 years. Patients and Methods Between 1987 and 1997, 3,449 patients age 50 to 81 years with operable breast cancer who had been taking 20 mg of tamoxifen for 2 years were randomly assigned to either stop or continue for an additional 3 years, if they were alive and recurrence free. Data on recurrences, new tumors, deaths, and cardiovascular events were obtained (April 2010). Results There were 1,103 recurrences, 755 deaths as a result of breast cancer, 621 cardiovascular (CV) events, and 236 deaths as a result of CV events. Fifteen years after starting treatment, for every 100 women who received tamoxifen for 5 years, 5.8 fewer experienced recurrence, compared with those who received tamoxifen for 2 years. The risk of contralateral breast cancer was significantly reduced (hazard ratio, 0.70; 95% CI, 0.48 to 1.00). Among women age 50 to 59 years, there was a 35% reduction in CV events (P = .005) and 59% reduction in death as a result of a CV event (P = .02); in older women, the effect was much smaller and not statistically significant. Conclusion Taking tamoxifen for the recommended 5 years reduces the risk of recurrence or contralateral breast cancer 15 years after starting treatment. It also lowers the risk of CV disease and death as a result of a CV event, particularly among those age 50 to 59 years. Women should therefore be encouraged to complete the full course. Although aromatase inhibitors improve disease-free survival, tamoxifen remains a cheap and highly effective alternative, particularly in developing countries.

Contralateral Breast Cancer in BRCA1 and BRCA2 Mutation Carriers

2004 ◽  
Vol 22 (12) ◽  
pp. 2328-2335 ◽  
Author(s):  
Kelly Metcalfe ◽  
Henry T. Lynch ◽  
Parviz Ghadirian ◽  
Nadine Tung ◽  
Ivo Olivotto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Contralateral Breast Cancer ◽  
Brca Mutation ◽  
Brca1 Mutation ◽  
Brca2 Mutation ◽  
Contralateral Breast ◽  
Second Primary ◽  
Brca1 And Brca2 ◽  
Breast Cancer Death ◽  
Actuarial Risk

Purpose To estimate the risk of contralateral breast cancer in BRCA1 and BRCA2 carriers after diagnosis and to determine which factors are predictive of the risk of a second primary breast cancer. Patients and Methods Patients included 491 women with stage I or stage II breast cancer, for whom a BRCA1 or BRCA2 mutation had been identified in the family. Patients were followed from the initial diagnosis of cancer until contralateral mastectomy, contralateral breast cancer, death, or last follow-up. Results The actuarial risk of contralateral breast cancer was 29.5% at 10 years. Factors that were predictive of a reduced risk were the presence of a BRCA2 mutation (v BRCA1 mutation; hazard ratio [HR], 0.73; 95% CI, 0.47 to 1.15); age 50 years or older at first diagnosis (v ≤ 49 years; HR, 0.63; 95% CI, 0.36 to 1.10); use of tamoxifen (HR, 0.59; 95% CI, 0.35 to 1.01); and history of oophorectomy (HR, 0.44; 95% CI, 0.21 to 0.91). The effect of oophorectomy was particularly strong in women first diagnosed prior to age 49 years (HR, 0.24; 95% CI, 0.07 to 0.77). For women who did not have an oophorectomy or take tamoxifen, the 10-year risk of contralateral cancer was 43.4% for BRCA1 carriers and 34.6% for BRCA2 carriers. Conclusion The risk of contralateral breast cancer in women with a BRCA mutation is approximately 40% at 10 years, and is reduced in women who take tamoxifen or who undergo an oophorectomy.

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