Occurrence Of Contralateral Breast Cancer Research Articles

Occurrence of contralateral breast cancer in a BRCA-positive breast cancer patient who underwent free TRAM flap reconstruction: a case report

This report presents a case of contralateral breast cancer in a BRCA mutation-positive patient who had previously undergone delayed free transverse rectus abdominis myocutaneous flap reconstruction for unilateral breast cancer. Having used up the available abdominal autologous tissue in the first reconstruction, a direct-to-implant procedure was employed for the reconstruction of the second, contralateral breast. Therefore, one breast was reconstructed using autologous tissue from the abdomen, while the other was asymmetrically reconstructed with an implant. If the risk of contralateral breast cancer had been anticipated initially, we might have opted for implant-based reconstruction from the start to facilitate a more symmetrical outcome in the event of subsequent contralateral reconstruction. This case underscores the importance of reviewing the risk of contralateral breast cancer in patients with unilateral breast cancer who also carry mutations in BRCA and other breast cancer susceptibility genes. Furthermore, it encourages consideration of how mutations in breast cancer susceptibility genes, including BRCA, influence the choice of plastic surgery reconstruction techniques. The findings from genetic testing for breast cancer susceptibility are now crucial to achieving aesthetic completeness in breast reconstruction.

Mammographic density changes after neoadjuvant chemotherapy in triple-negative breast cancer: Association with treatment and survival outcome

PurposeTo investigate the association of mammographic breast density with treatment and survival outcomes in patients with triple-negative breast cancer (TNBC) undergoing neoadjuvant chemotherapy (NAC). MethodsThis retrospective study evaluated 306 women with TNBC who underwent NAC followed by surgery between 2010 and 2019. The baseline density and the density changes after NAC were evaluated. Qualitative breast density (a-d) was evaluated using the Breast Imaging Reporting and Data System. Quantitative breast density (%) was evaluated using fully automated software (the Laboratory for Individualized Breast Radiodensity Assessment) in the contralateral breast. Multivariable logistic regression analysis was used to evaluate the association between breast density and pathologic complete response (pCR), stratified by menopausal status. Cox proportional hazard regression analysis was used to evaluate the association among breast density, the development of contralateral breast cancer, and the development of locoregional recurrence and/or distant metastasis. ResultsContralateral density reduction ≥10 % was independently associated with pCR in premenopausal women (odds ratio [OR], 2.5; p = 0.022) but not in postmenopausal women (OR, 0.9; p = 0.823). During a mean follow-up of 65 months, 10 (3 %) women developed contralateral breast cancer, and 68 (22 %) women developed locoregional recurrences and/or distant metastases. Contralateral density reduction ≥10 % showed no association with the occurrence of contralateral breast cancer (hazard ratio [HR], 3.1; p = 0.308) or with locoregional recurrence and/or distant metastasis (HR, 1.1; p = 0.794). ConclusionIn premenopausal women, a contralateral breast density reduction of ≥10 % after NAC was independently associated with pCR, although it did not translate into improved outcomes.

Age-Related Incidence and Peak Occurrence of Contralateral Breast Cancer

Age-Related Incidence and Peak Occurrence of Contralateral Breast Cancer

Age-Related Incidence and Peak Occurrence of Contralateral Breast Cancer

Young patients with breast cancer have higher risk for developing contralateral breast cancer (CBC) and have epidemiologic characteristics different from those of older patients. To examine the incidence and peak occurrence of CBC according to age at primary breast cancer (PBC) surgery. This cohort study included patients who were diagnosed with and underwent surgery for unilateral nonmetastatic breast cancer at Asan Medical Center, Korea, between January 1, 1999, and December 31, 2013, with follow-up through December 31, 2018. Data were analyzed from December 1, 2021, through April 30, 2023. Patients were divided into 2 groups according to their age at surgery for PBC: younger (≤35 years) vs older (>35 years). The main outcomes were cumulative incidence and hazard rate of CBC in the entire study population and in subgroups divided by cancer subtype, categorized according to hormone receptor (HR) and ERBB2 status. A total of 16 251 female patients with stage 0 to III breast cancer were analyzed; all patients were Korean. The mean (SD) age was 48.61 (10.06) years; 1318 patients (8.11%) were in the younger group, and 14 933 (91.89%) were in the older group. Median follow-up was 107 months (IQR, 79-145 months). Compared with the older group, the younger group had significantly higher incidence of CBC (10-year cumulative incidence, 7.1% vs 2.9%; P < .001) and higher risk (hazard ratio, 2.10; 95% CI, 1.62-2.74) of developing CBC. The hazard rate, which indicates risk for developing CBC at a certain time frame, differed according to the subtype of primary cancer. In patients with the HR+/ERBB2- subtype, the risk increased continuously in both age groups. In patients with the triple negative subtype, the risk increased until approximately 10 years and then decreased in both age groups. Meanwhile, in the HR-/ERBB2+ subtype, risk peaked earlier, especially in the younger group (1.7 years since first surgery in the younger group and 4.8 years in the older group). In this cohort study, patients aged 35 years or younger with breast cancer had a higher risk of developing CBC than older patients. Moreover, young patients with the HR-/ERBB2+ subtype tended to have a shorter interval for developing CBC. These findings might be useful in guiding treatment decisions, such as contralateral prophylactic mastectomy.

Association of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer-specific survival.

Breast cancer (BC) patients with a germline CHEK2 c.1100delC variant have an increased risk of contralateral BC (CBC) and worse BC-specific survival (BCSS) compared to non-carriers. To assessed the associations of CHEK2 c.1100delC, radiotherapy, and systemic treatment with CBC risk and BCSS. Analyses were based on 82,701 women diagnosed with a first primary invasive BC including 963 CHEK2 c.1100delC carriers; median follow-up was 9.1 years. Differential associations with treatment by CHEK2 c.1100delC status were tested by including interaction terms in a multivariable Cox regression model. A multi-state model was used for further insight into the relation between CHEK2 c.1100delC status, treatment, CBC risk and death. There was no evidence for differential associations of therapy with CBC risk by CHEK2 c.1100delC status. The strongest association with reduced CBC risk was observed for the combination of chemotherapy and endocrine therapy [HR (95% CI): 0.66 (0.55-0.78)]. No association was observed with radiotherapy. Results from the multi-state model showed shorter BCSS for CHEK2 c.1100delC carriers versus non-carriers also after accounting for CBC occurrence [HR (95% CI): 1.30 (1.09-1.56)]. Systemic therapy was associated with reduced CBC risk irrespective of CHEK2 c.1100delC status. Moreover, CHEK2 c.1100delC carriers had shorter BCSS, which appears not to be fully explained by their CBC risk.

Is bone mineral density a prognostic factor in postmenopausal women with luminal A breast cancer?

Several studies are concerned about the association between bone mineral density (BMD) and the risk of breast cancer in postmenopausal women, but it is controversial. Therefore, we evaluated whether BMD might be a risk factor for recurrences, or metastases in menopausal luminal A breast cancer patients. In this retrospective study, data of 348 patients with luminal A breast cancer who received treatment at Pusan National University Yangsan Hospital between 2012 and 2016 were analyzed. Patients were divided into two groups: normal BMD and low BMD including osteopenia or osteoporosis in preoperative examination. Patients were also divided into three groups according to BMD changes: no change in BMD; improvement in BMD, and deterioration in BMD. Events were defined as recurrence, occurrence of contralateral breast cancer, and metastasis to any other organ. Preoperative examination revealed normal BMD in 129 of 348 patients and low BMD in 219 patients. During a median follow-up period of 78 months, only 14 patients (4.0%) experienced recurrences, distant metastases, or occurrences of contralateral breast cancer. Five-year disease-free survival rate was 98.2% for 219 patients with low BMD and 95.0% for 129 patients with normal BMD (P=0.33). Disease-free survival at 5 years was 97.0% for the no change in the BMD group, 94.6% for the BMD improvement group, and 98.4% for the BMD deterioration group (P=0.79). In this study, BMD had no statistically significant associations on recurrences, metastases, or incidences of contralateral breast cancer in postmenopausal patients with luminal A breast cancer.

Tertiary Autologous Breast Reconstruction After Implant-Based Reconstruction: Safety and Patient-Related Outcomes

Silicone breast implants are popularly used for breast reconstruction. As more patients receive long-term silicone breast implants, the number of replacement operations will also increase, and some patients prefer to change from silicone breast implantation to tertiary autologous reconstruction. We evaluated the safety of tertiary reconstruction and assessed patient views regarding the two reconstruction methods. We retrospectively analyzed patient backgrounds, surgical characteristics, and silicone breast implantation retention periods until tertiary reconstruction. We designed an original questionnaire to assess patient opinion regarding silicone breast implantation and tertiary reconstruction. Twenty-three patients (24 breasts) with decisive factors of patient-initiated elective surgery (n=16), contralateral breast cancer occurrence (n=5), or late-onset infection (n=2) underwent tertiary reconstruction. The median time from silicone breast implantation to tertiary reconstruction was significantly shorter in patients with metachronous cancer (47 months) than that in those undergoing elective surgery (92 months). Complications included partial flap loss (n=1), seroma (n=6), hematoma (n=5), and infection (n=1). Total necrosis did not occur. Twenty-one patients responded to the questionnaire. The satisfaction score was significantly higher for abdominal flaps than for silicone breast implants. When presented with the option to select the initial reconstruction method again, 13 of 21 respondents chose silicone breast implantation. Tertiary reconstruction is beneficial because it reduces clinical symptoms and cosmetic complaints and is recommended as a bilateral reconstruction method, especially for patients with metachronous breast cancer. However, silicone breast implants, which are minimally invasive and associated with shorter hospital stays, were simultaneously found to be sufficiently attractive to patients.

Postoperative Adjuvant Anastrozole for 10 Rather than 5 Years in Patients with Oestrogen Receptor-Positive Breast Cancer: AERAS, a Randomised Multicentre Open-Label Phase III Trial

Background: Treatment with an aromatase inhibitor for 5 years is the standard treatment for postmenopausal hormone receptor-positive breast cancer. We investigated the effects of extending this treatment to 10 years on the risk of breast cancer recurrence. Methods: This prospective, randomised, multicentre open-label phase III study assessed the effect of extending anastrozole treatment for an additional 5 years in postmenopausal patients with stage I–IIIA hormone receptor-positive breast cancer who were disease-free after treatment with either 5 years of anastrozole alone or 2–3 years of tamoxifen followed by 2–3 years of anastrozole. Patients were allocated randomly (1:1) to continue anastrozole (1 mg/day orally) for an additional 5 years or stop anastrozole, using the central computer at the Comprehensive Support Project for Oncology Research Data Centre. Randomisation was stratified by type of postoperative endocrine therapy, nodal status, prior adjuvant chemotherapy, and facility. The primary endpoint was disease-free survival, including breast cancer recurrence, second primary cancers, and death from any cause. This study is registered with UMIN clinical trials registry, number UMI00818. Findings: We enrolled 1697 patients from 117 facilities between November 2007 and November 2012. Patients were assigned randomly to the continue group (n=849) or the stop group (n=848). Follow-up information was available for 1593 patients (n=787 in the continue group, n=806 in the stop group) as the full analysis set. After a median follow-up of 5·1 years, there were 172 events involving disease recurrence or the occurrence of contralateral breast cancer (75 in the continue group and 97 in the stop group) and 40 deaths (21 in the continue group and 19 in the stop group). The 5-year disease-free survival rates were 91% (95% confidence interval [CI] 89–93) in the continue group and 86% (95% CI 83–88) in the stop group (hazard ratio [HR] for disease-free survival 0·61, 95% CI 0·46–0·82; p<0·0010, two-sided log-rank test). The 5-year overall survival rates were 98% in the continue group and 98% in the stop group (HR 1·13, p=0·7042). The 5-year distant disease-free survival rates were 95% in the continue group and 93% in the stop group (HR 0·68, p=0·0553). Sixty-seven second primary cancers occurred, including 24 in the continue group and 43 in the stop group. Menopausal or bone-related all-grade adverse events were more frequent among patients in the continue group than in the stop group, including higher incidences of hot flashes (111 [14%] vs 81 [10%]), stiff joints (162 [21%] vs 98 [12%]), arthralgia (294 [37%] vs 236 [29%]), and new-onset osteoporosis (370 [47%] vs 355 [44%]). Interpretation: Continuing adjuvant anastrozole for an additional 5 years after 5 years’ initial treatment with anastrozole or tamoxifen is safe and beneficial in postmenopausal patients with hormone receptor-positive breast cancer. Trial Registration: This study is registered with UMIN clinical trials registry, number UMI00818. Funding: The Comprehensive Support Project for Oncology Research of the Public Health Research Foundation Declaration of Interest: None to declare. Ethical Approval: Ethical approval was provided by local ethics committees in each hospital.

Molecular Features and Functional Implications of Germline Variants in Triple-Negative Breast Cancer.

The germline variant spectrum of triple-negative breast cancer (TNBC) is different from that of other subtypes and has demonstrated ethnic differences. However, the germline variants of TNBC among Chinese patients and its clinical significance remain unclear. Using our multi-omics TNBC cohort (n = 325), we determined the spectrum of germline variants in TNBC and aimed to illustrate their biological and clinical implications. Overall, 16.0% (52 of 325) of TNBC patients harbored at least 1 pathogenic or likely pathogenic germline variant. These germline variants were associated with early onset of TNBC, the occurrence of contralateral breast cancer, the basal-like immune-suppressed mRNA subtype, and the homologous recombination deficiency (HRD) mutation subtype. Somatic allele-specific imbalance was observed in 54.1% of these germline variants, which was correlated with early onset of breast cancer and elevated HRD. The genes BRCA1 (7.4%), RAD51D (2.8%), and BRCA2 (2.2%) were those most frequently mutated. The RAD51D germline variants, especially K91fs, were enriched in Chinese patients with TNBC compared with Caucasian and African American patients. The Chinese-specific RAD51D germline variants were functionally associated with the instability of the RAD51D protein, HRD, and sensitivity to PARP inhibitors. Chinese TNBC patients have a distinct spectrum of germline variants, with a remarkable impact on the clinical and molecular characteristics of the tumor. Integrative germline-somatic analysis may help identify TNBC patients who are most likely to be affected by their germline variants and in performing clinical interventions more precisely. The RAD51D variants enriched in our cohort may serve as therapeutic targets and guide precision treatment of TNBC.

Abstract P5-03-06: Comparison of clinicopathological features and outcome of breast cancer in BRCA-mutation carriers, in patients with a family history without BRCA-mutation and in patients with sporadic disease

Abstract BACKGROUND: BRCA1 and BRCA2 are two major susceptibility genes for breast cancer. We aimed to compare clinicopathological features and outcomes in BRCA1/2-mutation carriers patients, in patients with a family history suggesting hereditary breast cancer (HBC) without BRCA mutation (Eisinger score ≥ 5), and in patients with sporadic disease. METHODS: We retrospectively reviewed clinical and pathological data of 56 BRCA-mutation carriers (29 BRCA1, 27 BRCA2), 85 HBC patients and 70 sporadic breast cancer patients treated at Saint-Louis hospital between 1987 and 2017. Sporadic breast cancer patients were free from family history of cancer and randomly extracted from our database. We recorded age, clinicopathological features of breast tumors (tumor size, grade, nodal status, hormone receptor and c-erbB2 status), treatment type, ipsilateral relapse, contralateral breast cancer occurrence, distant metastasis and outcome (disease-free and overall survival). RESULTS: BRCA-mutated and HBC patients showed earlier age of onset of tumor (respectively 36, 42 and 40 years) than sporadic breast cancer patients (54 years, p&amp;lt;0.05). Relatives of HBC patients have developed significantly more different tumor-types than BRCA-mutated patient. BRCA1-mutated patients tumors were mostly triple-negative (62%, p&amp;lt;0,05) and grade 3 (83%, p&amp;lt;0,05), whereas the other groups presented mostly tumors of luminal subtype and grade 2. Of note, HBC and BRCA2-mutated patients shared similar clinical and pathological characteristics. Interestingly, HER2 overexpressed tumors were less represented in BRCA-mutated patients (4 and 10%) than in HBC and sporadic breast cancer patients (22% and 19%, p=0,06). BRCA1-mutated tumors were significantly more sensitive to chemotherapy, with a higher rate of clinicopathological complete response to neo-adjuvant chemotherapy (64%, p&amp;lt;0.05). BRCA1-mutated patients developed more contralateral breast cancers than sporadic breast cancer patients (p=0,01). No difference in RFS, DFMS or OS was observed between the different groups. CONCLUSION: clinicopathological characteristics and outcomes of HBC patients are similar to those of BRCA2-mutated patients. Ongoing multi-gene panel testing in this population will identify mutations in other relevant genes and provide new insights in genotype-phenotype correlation. Citation Format: Stéphanie Bécourt, Ludovic Doucet, Odile Cohen-Haguenauer, Florence Ledoux, Olivia Nguyen, Luca Campedel, Sylvie Giacchetti, Caroline Cuvier, Marc Espié, Luis Teixeira. Comparison of clinicopathological features and outcome of breast cancer in BRCA-mutation carriers, in patients with a family history without BRCA-mutation and in patients with sporadic disease [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-03-06.

Abstract GS3-04: A prospective randomized multi-center open-label phase III trial of extending aromatase-inhibitor adjuvant therapy to 10 years - Results from 1697 postmenopausal women in the N-SAS BC 05 trial: Arimidex extended adjuvant randomized study (AERAS)

Abstract Background: Treatment with an aromatase inhibitor for 5 years as up-front monotherapy or after tamoxifen therapy for 2-3 years is the treatment of choice for hormone-receptor-positive breast cancer in postmenopausal women. Extending treatment with an aromatase inhibitor to 10 years may reduce the risk of breast cancer recurrence. Methods: We conducted a prospective randomized multi-center open-label phase III trial to assess the effect of the extended use of anastrozole for an additional 5 years. Postmenopausal patients with stageI-III, hormone-receptor-positive breast cancer, disease-free after 5 years of either anastrozole alone or tamoxifen 2-3 years followed by anastrozole 3-2 years were randomized to continual group with anastrozole for an additional 5 years or stop group without an additional anastrozole. Our primary end point was disease-free survival. Results: We enrolled 1697 women. After a median follow up of 4.9 years, there were 149 events involving disease recurrence or the occurrence of contralateral breast cancer (51 in continual group and 98 in stop group) and 7 deaths (3 in continual group and 4 in stop group). The 5-year disease-free survival rate was 91.9% (95% confidence interval [CI], 89.4 to 93.8) in continual group and 84.4% (95% CI: 80.0 to 88.0) in stop group (hazard ratio for disease-free survival,0.548 ;P=0.0004. by a two-sided log-rank test stratified according to nodal status, prior adjuvant chemotherapy, institution, and choice of anastrozole or tamoxifen). The rate of 5-year overall survival was 99.5% in continual group and 99.6% in stop group. (hazard ratio,1.389 ;P=0.665). The rate of 5-year distant disease-free survival was 97.2% in continual group and 94.3% in stop group (hazard ratio,0.514 ;P=0.0077). Bone-related adverse events were observed more frequently among patients in continual group than among patients in stop group, including a higher incidence of bone pain, stiff joints, bone fractures, and new-onset osteoporosis. Conclusion: The extension of treatment with an adjuvant aromatase inhibitor (anastrozole) to 10 years resulted in significantly higher rates of disease-free survival and distant disease-free survival than those with no additional anastrozole, but the rate of overall survival was not different between two groups. Our study shows that it is safe and beneficial for postmenopausal patients with hormone-receptor-positive breast cancer to take an anastrozole as adjuvant therapy for an additional 5 years after initial treatment. (UMIN:000000818) Citation Format: Ohtani S, Iijima K, Higaki K, Sato Y, Hozumi Y, Hasegawa Y, Takei H, Tanaka M, Yagata H, Masuoka H, Tanabe M, Egawa C, Komoike Y, Saji S, Nakamura T, Yanagita Y, Ohtsu H, Mukai H, Iwase T. A prospective randomized multi-center open-label phase III trial of extending aromatase-inhibitor adjuvant therapy to 10 years - Results from 1697 postmenopausal women in the N-SAS BC 05 trial: Arimidex extended adjuvant randomized study (AERAS) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS3-04.

Trends in contralateral prophylactic mastectomy rate according to clinicopathologic and socioeconomic status.

PurposeThere has been an increasing trend in the use of contralateral prophylactic mastectomy (CPM) among women diagnosed with unilateral breast cancer or mutations in BRCA1 or BRCA2 to reduce the occurrence of contralateral breast cancer. This study aimed to examine trends in the CPM rate according to clinicopathologic and socioeconomic status at a single institution in Korea.MethodsThis study included 128 patients with mutations in BRCA1 or BRCA2. Patients were divided into a CPM group (n = 8) and a non-CPM group (n = 120) between May 2013 and March 2016. The main outcome variables, including epidemiology, clinical features, socioeconomic status, and tumor characteristics, were analyzed.ResultsA total of 8 CPMs were performed among 128 patients. All CPM patients were married. The proportion of professional working women was higher in the CPM group (P = 0.049). Most patients who underwent CPM graduated college, compared to less than a third of the non-CPM group (P = 0.013). The CPM group had a higher rate of visits to the Hereditary Breast and Ovarian Cancer (HBOC) clinic (P = 0.021). The risk-reducing salpingo-oophorectomy (RRSO) rate was significantly higher in the CPM group (P < 0.01).ConclusionCPM rates were significantly different according to socioeconomic status. The CPM rate tends to increase in highly educated and professional working women. The socioeconomic status of patients is an important factor in the decision to participate in the HBOC clinic and undergo CPM or RRSO.

Age-related risk factors associated with primary contralateral breast cancer among younger women versus older women.

Contralateral prophylactic mastectomy is increasing, despite unclear evidence of improving survival. To investigate the age-related risk factors for contralateral breast cancer (CBC). This study included 8716 patients diagnosed with non-metastatic unilateral invasive breast cancer between 1989 and 2008. Data on primary tumor size, node metastasis, grade and subtype using individual matching were used to adjust for differences in the primary tumor and treatment between younger and older age groups. CBC risk factors, CBC-free survival, and annual CBC risk were analyzed by age. The younger group included 652 patients aged under 35 years, and the older group included 2608 women aged 35years or older. The median time to CBC development was 6.1years. CBC was detected in 6.6% of the women in the younger group and 2.5% of those in the older group. Multivariable analysis revealed a relative CBC risk of 2.48 in younger women compared to older women. The risk was significantly higher among women with human epidermal growth factor receptor 2 (HER2)-overexpressing tumors (hazard ratio [HR] 4.98), a family history of breast cancer (HR 7.79), and anti-hormone therapy (HR 3.46). In younger women with HER2-positive cancer, CBC occurrence peaked at 4.6years after surgery, in those with hormone receptor-positive cancer, it peaked at 7.1years after surgery, and in triple-negative disease cases, and it increased steadily over time. After adjusting for primary breast tumor characteristics, patients < 35years old had 2.5 times the risk of CBC development compared to the older women. CBC occurrence peaked within 5years after primary breast cancer in younger women with the HER2-positive subtype and after 5years in cases with the hormone receptor-positive subtype.

Low-dose aspirin use and risk of contralateral breast cancer: a Danish nationwide cohort study

Observational studies of aspirin use and breast cancer risk have provided inconsistent results. The occurrence of contralateral breast cancer (CBC) among breast cancer survivors may serve as a useful high-risk model to identify preventive drug effects. Using this model, we examined the association between post-diagnosis use of low-dose aspirin and risk of CBC. We identified all women recorded with a first primary breast cancer in the Danish Breast Cancer Cooperative Group Database between 1996 and 2012. Information on drug use, tumor and patient characteristics, treatment, and CBC was obtained from nationwide registries. In the main analysis, we defined time-varying post-diagnosis low-dose aspirin use as two or more prescriptions filled during follow-up and applied a one-year exposure lag. Cox proportional hazard regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between post-diagnosis low-dose aspirin use and CBC risk. Among 52,723 breast cancer patients, 1,444 women developed CBC during a median follow-up of 4.8 years. The adjusted HR for CBC associated with post-diagnosis use of low-dose aspirin was 0.91 (95% CI: 0.75–1.09). We observed no substantial variation in HRs according to pattern of low-dose aspirin use or estrogen receptor status of the first or the contralateral breast cancer. In conclusion, this large nationwide cohort study of breast cancer survivors does not provide strong evidence suggesting an association between post-diagnosis use of low-dose aspirin and risk of CBC.

Patterns of Occurrence and Outcomes of Contralateral Breast Cancer: Analysis of SEER Data.

Population-based estimates are lacking for the temporal trends in the contralateral breast cancer (CBC) risk for patients with breast cancer (BC). Data for BC patients diagnosed with CBC were collected from the Surveillance, Epidemiology, and End Results database. CBC incidence was calculated using the Kaplan-Meier method and the temporal trend in CBC incidence was assessed using joinpoint regression. Survival analysis was calculated using propensity scoring (PS) and multivariate Cox regression with a competing risk model. We found that 10,944 of 212,630 patients with early-stage BC were subsequently diagnosed with secondary BC in the contralateral breast. The 5-, 10-, 15-, and 20-year cumulative CBC incidences were 1.9, 4.6, 7.6, and 10.5%, respectively. Being younger (<40 years), black, hormone receptor-negative, and having undergone radiotherapy were correlated with a high risk of CBC occurrence. CBC incidence increased continuously in the first 11 years after the initial cancer diagnosis, and the upward trend slowed from years 11 to 21, and tended to decline from years 21 to 24. CBC diagnosis was significantly and negatively associated with survival. We reported population-based estimates of the CBC occurrence pattern and risk factors. Patients are at high risk of developing CBC in the first 21 years after the initial BC diagnosis.

Extending Aromatase-Inhibitor Adjuvant Therapy to 10 Years

BackgroundTreatment with an aromatase inhibitor for 5 years as up-front monotherapy or after tamoxifen therapy is the treatment of choice for hormone-receptor–positive early breast cancer in postmenopausal women. Extending treatment with an aromatase inhibitor to 10 years may further reduce the risk of breast-cancer recurrence.MethodsWe conducted a double-blind, placebo-controlled trial to assess the effect of the extended use of letrozole for an additional 5 years. Our primary end point was disease-free survival.ResultsWe enrolled 1918 women. After a median follow-up of 6.3 years, there were 165 events involving disease recurrence or the occurrence of contralateral breast cancer (67 with letrozole and 98 with placebo) and 200 deaths (100 in each group). The 5-year disease-free survival rate was 95% (95% confidence interval [CI], 93 to 96) with letrozole and 91% (95% CI; 89 to 93) with placebo (hazard ratio for disease recurrence or the occurrence of contralateral breast cancer, 0.66; P=0.01 by a two-sided log-rank test stratified according to nodal status, prior adjuvant chemotherapy, the interval from the last dose of aromatase-inhibitor therapy, and the duration of treatment with tamoxifen). The rate of 5-year overall survival was 93% (95% CI, 92 to 95) with letrozole and 94% (95% CI, 92 to 95) with placebo (hazard ratio, 0.97; P=0.83). The annual incidence rate of contralateral breast cancer in the letrozole group was 0.21% (95% CI, 0.10 to 0.32), and the rate in the placebo group was 0.49% (95% CI, 0.32 to 0.67) (hazard ratio, 0.42; P=0.007). Bone-related toxic effects occurred more frequently among patients receiving letrozole than among those receiving placebo, including a higher incidence of bone pain, bone fractures, and new-onset osteoporosis. No significant differences between letrozole and placebo were observed in scores on most subscales measuring quality of life.ConclusionsThe extension of treatment with an adjuvant aromatase inhibitor to 10 years resulted in significantly higher rates of disease-free survival and a lower incidence of contralateral breast cancer than those with placebo, but the rate of overall survival was not higher with the aromatase inhibitor than with placebo. (Funded by the Canadian Cancer Society and others; ClinicalTrials.gov numbers, NCT00003140 and NCT00754845.)

Preoperative breast magnetic resonance imaging and contralateral breast cancer occurrence among older women with ductal carcinoma in situ.

Although preoperative magnetic resonance imaging (MRI) can detect mammographically occult contralateral breast cancers (CBCs) among women with ductal carcinoma in situ (DCIS), the impact of MRI on the incidence of subsequent CBC events is unclear. We examined whether MRI use decreases CBC occurrences and detection of invasive disease among women who develop a CBC. Utilizing the Surveillance, Epidemiology, and End Results-Medicare dataset, we assessed overall, synchronous (<6months after primary cancer diagnosis), and subsequent (≥6months after diagnosis, i.e., metachronous) CBC occurrence in women aged 67-94years diagnosed with DCIS during 2004-2009, with follow-up through 2011. We applied a matched propensity score approach to compare the stage-specific incidence rate of CBC according to MRI use. Our sample consisted of 9166 beneficiaries, 1258 (13.7%) of whom received preoperative MRI. After propensity score matching, preoperative MRI use was significantly associated with a higher synchronous CBC detection rate (108.6 vs. 29.7 per 1000 person-years; hazard ratio [HR]=3.65; p<.001) with no significant differences in subsequent CBC rate (6.7 vs. 6.8 per 1000 person-years; HR=0.90; p=.71). The 6-year cumulative incidence of any CBC (in situ plus invasive) remained significantly higher among women undergoing MRI, compared with those not undergoing MRI (9 vs. 4%, p<.001). Women undergoing MRI also had a higher incidence of invasive CBC (4 vs. 3%, p=.04). MRI use resulted in an increased detection of synchronous CBC but did not prevent subsequent CBC occurrence, suggesting that many of the undetected CBC lesions may not become clinically evident.

Contralateral breast cancer: incidence according to ductal or lobular phenotype of the primary

To identify differences in the incidence of contralateral breast cancer between patients with a primary tumour diagnosis of invasive ductal carcinoma (IDC) and those with a diagnosis of invasive lobular carcinoma (ILC). Data from two large cancer registries (registry A & B) the Northern and Yorkshire Cancer Registry Information Service (NYCRIS) and the West Midlands Cancer Intelligence Unit (WMCIU) from 1998-2003 for all cases of invasive breast cancer of either pure ductal or pure lobular reported histology were obtained. The invasive status of the contralateral tumour diagnosis and tumour morphology was collected. Chi-square tests were undertaken to examine the differences in contralateral rates for both registries and univariate analysis to ascertain which predictors affected contralateral breast cancer risk for registry A the WMCIU cases. A total of 38,132 patients were studied, 32,735 patients with IDC and 5397 (14.2%) patients with ILC over the 6-year period. There was no significant difference between the occurrence and time to occurrence of contralateral breast cancer according to original cancer histology, 901 (2.8%) patients with IDC versus 166 (3.1%) patients with ILC (p=0.169). The analysis of registry A cases showed no association between original histology (ductal versus lobular), age at diagnosis, tumour grade, use of radiotherapy for the primary cancer or use of systemic therapy (chemotherapy and/or endocrine therapy), and development of a contralateral breast cancer. There is no apparent increase in risk of developing a contralateral breast cancer according to the primary cancer histology either IDC or ILC. Standard mammographic follow-up does not need to take account of original tumour pathology. Increased intervention or post-treatment surveillance for the contralateral breast is not indicated in the context of ILC. The role of MRI should be restricted to those patients with ILC who are planning breast-conservation surgery, but not for assessing the contralateral breast.

Preoperative Breast Magnetic Resonance Imaging and Contralateral Breast Cancer Occurrence Among Older Women With Breast Cancer.

Preoperative magnetic resonance imaging (MRI) detects occult contralateral breast cancers (CBCs) in women with breast cancer, but the impact of detection on long-term CBC events is unclear. We examined whether MRI use decreases the occurrence of CBCs and the detection of stages II to IV disease among women who develop a CBC. Analyzing the SEER-Medicare database, we assessed overall, synchronous (< 6 months after primary cancer diagnosis), and subsequent (ie, metachronous) stage-specific CBC occurrences in women who were diagnosed with stages I and II breast cancer during 2004-2009 and who were observed through 2011. Among 38,971 women with breast cancer, 6,377 (16.4%) received preoperative MRI. After propensity score matching, and compared with women who did not undergo MRI, preoperative MRI use was significantly associated with a higher synchronous CBC detection rate (126.4 v 42.9 per 1,000 person-years, respectively; hazard ratio, 2.85; P < .001) but a lower subsequent CBC detection rate (3.3 v 4.5 per 1,000 person-years, respectively; hazard ratio, 0.68; P = .002). However, the 5-year cumulative incidence of CBC remained significantly higher among women undergoing MRI compared with those not undergoing MRI (7.2% v 4.0%, respectively; P < .001). The analyses of projected CBC events for 10,000 patients who receive MRI indicated that, after a 5-year follow-up, MRI use would detect an additional 192 in situ CBCs (95% CI, 125 to 279) and 120 stage I CBCs (95% CI, 62 to 193) but would not have a significant impact on stages II to IV CBC occurrences (∼ 6; 95% CI, -21 to 47). An increased synchronous CBC detection rate, attributable to MRI, was not offset by a decrease of subsequent CBC occurrence among older women with early-stage breast cancer, suggesting that preoperative MRI in women with breast cancer may lead to overdiagnosis.

Contralateral breast cancer: a clinico-pathological study of second primaries in opposite breasts after treatment of breast malignancy.

Breast cancer is by far the most frequent cancer of women (23 % of all cancers), ranking second overall when both sexes are considered together. Contralateral breast cancer (CBC) is becoming an important public health issue because of the increased incidence of primary breast cancer and improved survival. The present communication concerns a study to evaluate the role of various clinico-pathological factors on the occurrence of contralateral breast cancer. A detailed analysis was carried out with respect to age, menopausal status, family history, disease stage, surgery performed, histopathology, hormone receptor status, and use of chemotherapy or hormonal therapy. The diagnosis of CBC was confirmed on histopathology report. Relative risk with 95%CI was calculated for different risk factors of contralateral breast cancer development. CBC was found in 24 (4.5%) out of 532 patients. Mean age of presentation was 43.2 years. Family history of breast cancer was found in 37.5% of the patients. There was statistically significant higher rate (83.3%) of CBC in patients in age group of 20-40 years with RR=11.3 (95% CI: 1.4, 89.4, p=0.006) seen in 20-30 years and RR=10.8 (95% CI:1.5-79.6, p=0.002) in 30-40 years as compared to older age of 60-70 years. Risk of development was higher in premenopausal women (RR=8.6, 95% CI: 3.5-21.3, p≤0.001). Women with family history of breast cancer had highest rate (20.9%) of CBC (RR=5.4, 95% CI: 2.5-11.6, p≤0.001). Use of hormonal therapy in hormone receptor positive patients was protective factor in occurrence of CBC but not significant (RR=0.7, 95% CI: 0.3-1.5, p=0.333). Younger age, premenopausal status, and presence of family history were found to be significant risk factors for the development of CBC. Use of hormonal therapy in hormone receptor positive patients might be protective against occurrence of CBC but did not reach significance.