Diagnosis Of Contralateral Breast Cancer Research Articles

Detection of contralateral breast cancer in patients with primary breast cancer through AI-assisted mammography.

e13645 Background: Survivors of breast cancer are at an elevated risk for developing contralateral breast cancer (CBC), a risk that surpasses the incidence of initial primary breast cancer within the general population. Consequently, annual mammography screenings are advocated to monitor for ipsilateral recurrence and the emergence of CBC. However, the sensitivity of surveillance mammography exhibits considerable variation, ranging between 45% and 90%, with notably lower detection rates in younger individuals and those with dense breast tissue. This study explores the efficacy of an artificial intelligence (AI) detection algorithm in mammography for the early identification of CBC prior to the official diagnosis. Methods: A retrospective analysis was conducted on patients treated for primary breast cancer from 2000 to 2021 at Seoul National University Hospital. This involved reviewing serial mammograms post-surgery and adjuvant therapy from 460 patients who subsequently developed CBC (CBC group) and 469 patients who did not (control group). These mammograms were evaluated using the Lunit INSIGHT mammogram AI system, which provides a pixel-level abnormality score between 0 and 100, with higher scores indicating increased abnormality. Scores exceeding 10 were considered indicative of CBC, reflecting a 90% sensitivity based on the AI software's tuning dataset. The diagnostic accuracy of AI-assisted mammography was then juxtaposed with that of specialist radiologists' evaluations. Results: At the point of CBC diagnosis, the median AI abnormality score was markedly higher in the CBC group (22.9 [IQR, 2.1-81.1]) compared to the control group's final follow-up mammogram (0.4 [IQR, 0.1-1.5], p<0.001). The AI system's sensitivity for CBC detection paralleled that of radiologist assessments (59.6% for AI vs. 56.5% for radiologists out of 460 detected cancers), with the AI method achieving an AUROC of 0.836 and a specificity of 91.0%. Notably, AI detected 84 cases (30.7%) at least six months and 59 cases (21.5%) more than a year before the official CBC diagnosis. Conclusions: The application of AI in mammography screening has demonstrated significant potential for the early detection of CBC, identifying cases up to a year before formal diagnosis. This underscores the value of integrating AI tools in mammography to enhance early detection rates of CBC among primary breast cancer patients.

Breast Cancer in the Tissue of the Contralateral Breast Reduction

Breast cancer is the most prevalent malignancy among women worldwide, and the increasing number of survivors is due to advances in early diagnosis and treatment efficacy. Consequently, the risk of developing contralateral breast cancer (CBC) among these survivors has become a concern. While surgical intervention with lumpectomy is a widely used primary approach for breast cancer, post-operative breast asymmetry is a potential concern. Many women opt for symmetrizing reduction procedures to improve aesthetic outcomes and quality of life. However, despite careful radiological screening, there is a chance of accidentally finding CBC. To address this, tissue excised during symmetrizing surgery is examined pathologically. In some cases, CBC or in situ lesions have been incidentally discovered in these specimens, prompting a need for a more thorough examination. Resection in pieces and the absence of surgical marking and pathological inking of the margin have made it challenging to precisely identify tumor location and assess tumor size and margin status, hampering adjuvant treatment decisions. A new protocol introduced in July 2022 aims to enhance the precision of CBC diagnosis, allowing for tailored treatment plans, including re-excision, systemic adjuvant therapy, or radiation therapy.

Abstract P3-04-11: Longitudinal Changes of Contralateral Breast Mammographic Artificial Intelligence Algorithms Score in Ductal Carcinoma In Situ patient with Tamoxifen

Abstract Background Mammographic Artificial intelligence (AI) algorithms (Lunit insight MMG) draws attention as a diagnostic support tool for breast cancer detection. Lunit insight MMG provides a location suspected of breast cancer with a heatmap and a score reflecting the probability of the presence of suspicious areas. We investigated whether the Lunit insight MMG score is relevant for predicting the response to adjuvant tamoxifen. Methods Patients diagnosed with DCIS and underwent treatment at Seoul National University Hospital in 2010 were retrospectively enrolled. Clinical characteristics, tamoxifen use, survival data, and mammography images were extracted from the electronic medical records, and Lunit insight MMG scores were calculated retrospectively. We classified two groups according to tamoxifen treatment and compared the score change of contralateral breast from baseline to 5 years after surgery for DCIS. Change categories of Lunit insight MMG score included maintaining high risk, maintaining low risk, increasing from low risk to high risk, and decreasing from high risk to low risk. Results Of 100 patients, 50 (50%) had undergone tamoxifen treatment (group 1) and 50 (50%) had not (group 2). The median age of the patients was 48.4 years for group 1 and 51.5 years for group 2 (p=0.172). The median follow-up duration was 8.7 years for the whole cohort. Using Lunit insight MMG score, more patients in group 1 decreased in contralateral breast cancer (CBC) risk compared with group 2 (6.0% vs. 2.0%; P=.008). No patients in group 1 had an increase in CBC risk while 9 patients increased in group 2 (0% vs. 18.0%; P =.008). There was no ipsilateral breast cancer recurrence for the whole cohort, and two patients experienced contralateral invasive breast cancer in group 2. In two patients with CBC, the Lunit insight MMG score increased five years after surgery, one year and three years before the CBC diagnosis. Conclusions Longitudinal Changes of Mammographic AI algorithms Score may be a predictive surrogate marker for response to tamoxifen therapy in hormone receptor-positive DCIS. Citation Format: Changjin Lim, Eun Kyung Park, Hong-Kyu Kim, Eunhye Kang, Ji-Jung Jung, Hyunsu Yeoh, Jang-il Kim, Jung Whan Chun, Han-Byoel Lee, Hyeong-Gon Moon, Wonshik Han. Longitudinal Changes of Contralateral Breast Mammographic Artificial Intelligence Algorithms Score in Ductal Carcinoma In Situ patient with Tamoxifen [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-04-11.

Aromatase inhibitors and contralateral breast cancer in BRCA mutation carriers.

Deleterious BRCA mutations confer a significant lifetime risk of breast cancer (BC) as well as contralateral BC (CBC) in patients who do not undergo prophylactic mastectomy. Prior reports have suggested that tamoxifen reduces the risk of CBC in BRCA mutation carriers. Whether aromatase inhibitors (AI) have the same effect is unknown. This is a retrospective review of patients diagnosed with non-metastatic ER+ BC between 2004 and 2014 with known BRCA mutation status. Patients were followed from primary diagnosis until CBC diagnosis or death. Median follow-up was 11.5years. Risk of CBC was evaluated as time to event. 935 subjects were included in this analysis, with 53 BRCA1 mutation carriers, and 94 BRCA2 mutation carriers. Median age at diagnosis was 42.7years. Seventy-two percent (676) received tamoxifen and 43% (405) received AI. A total of 66 CBCs occurred, of which 10% (15/147) occurred in BRCA mutation carriers vs 6.5% (51/788) in BRCA wild type. Multivariate analyses indicated that BRCA status and AI use were significantly associated with CBC risk. AI use resulted in a significant reduction in risk of CBC (HR 0.44, p = 0.004) regardless of the BRCA mutation status. Tamoxifen use was not associated with reduced risk of CBC. This is the first report showing that AIs reduce the risk of CBC in BRCA mutation carriers. The potential role of AIs as chemoprevention should be validated in larger independent cohorts.

Effect of breast-conserving surgery plus radiotherapy versus mastectomy on breast cancer-specific survival for early-stage contralateral breast cancer.

Breast-conserving surgery followed by radiotherapy is recommended in most women with early-stage unilateral breast cancer. However, its role in contralateral breast cancer (CBC) patients remains unclear. This retrospective study aimed to evaluate the breast cancer-specific survival (BCSS) outcomes after breast-conserving surgery plus radiotherapy compared with mastectomy in women with early-stage (T1-2N0-1M0) CBC. Data were extracted from the Surveillance, Epidemiology, and End Results database. BCSS was analyzed using the log-rank method, competing risks regression model, and propensity score matching method. A total of 9,336 early-stage CBC patients were included. After multivariable adjustment, no significant difference in BCSS was found between early-stage CBC patients undergoing breast-conserving surgery plus radiotherapy and those undergoing mastectomy [hazard ratio (HR) 1.11, 95% confidence interval (CI): 0.90-1.37, P=0.329]. BCSS was similar in both treatment groups and in the subgroups stratified by age at first primary breast cancer or CBC diagnosis (≤50, 51-60, and >60 years), time interval between cancers (<0.25, 0.25-4, 5-9, and ≤10 years), stage of first primary breast cancer, T classification of CBC, histology and hormone receptors status of both cancers (all P>0.05). Among patients with N1 disease at CBC diagnosis, breast-conserving surgery plus radiotherapy was associated with a boundary significantly improved BCSS (HR 1.45, 95% CI: 1.00-2.12, P=0.050). Among patients who underwent breast-conserving surgery for first primary cancer, bilateral mastectomy for contralateral cancer did not improve BCSS compared with breast-conserving surgery plus radiotherapy (P>0.05). There was no significant difference in BCSS between breast-conserving surgery plus radiotherapy and mastectomy plus radiotherapy (P>0.05). Stable results were obtained after propensity score matching. Breast-conserving surgery plus radiotherapy did not significantly influence BCSS outcomes of patients with early-stage CBC. Bilateral mastectomy and mastectomy plus radiotherapy did not confer a survival advantage over breast-conserving surgery plus radiotherapy in these patients. Future prospective studies are necessary to expand on these results.

Invasive Lobular Breast Cancer: Data to Support Surgical Decision Making

Invasive lobular carcinoma (ILC) is thought be a unique entity with higher rates of multifocal/multicentric and bilateral disease. This study aimed to evaluate the true extent of the disease, risk of bilaterality, lymph node involvement, and impact of preoperative imaging to help guide surgical decisionmaking. A retrospective analysis identified patients treated for ILC between 2004 and 2017. Clinical staging and pathologic results were compared. Follow-up details including local recurrence, contralateral breast cancer (CBC), and survival outcomes were evaluated. The study identified 692 patients with ILC, including 43 patients (6%) with a diagnosis of CBC and 232 patients (33%) with a diagnosis of multifocal/multicentric disease at presentation. Preoperative magnetic resonance imaging (MRI) led to an identification of additional disease in 20% of the patients. Preoperative MRI resulted in a more accurate prediction of tumor size staging but did not improve the discordance between clinical and pathologic nodal staging. Overall, the rate of imaging occult lymph node disease was 24%. At the 6-year follow-up evaluation, a local recurrence had developed in 2.3%, a CBC in 2.3, and a distant metastasis in 9.4% of the patients. The overall survival rate was 96% at 3 years and 91% at 5 years. Invasive lobular carcinoma is a distinct subset of cancer that poses a diagnostic staging challenge. The results of this study favor MRI for accurate tumor staging and for improving detection of multicentricity and bilaterality. However, clinicians should be aware of the higher likelihood of occult lymph node involvement with ILC and subsequent early metastasis.

Abstract P1-17-10: Breast pain is a common complaint after breast cancer treatment but not a sign of recurrence

Abstract Background: Mastalgia, breast pain without other signs or symptoms, is a very common complaint, yet occurs in only approximately 5% of patients with breast cancer. Most clinicians are aware of this lack of association with cancer. Mastalgia is also a common complaint after breast cancer treatment. This symptom is very worrisome to many women, and when seen in the office, clinicians tend to give in to the fear of patients and order various tests. In 2017, we presented an abstract at SABCS that showed that breast pain was not associated with breast cancer diagnosis. Many attendees were interested in the incidence of breast pain after breast cancer treatment. The current study was performed to evaluate the incidence and significance of mastalgia after breast cancer treatment. Methods: Maricopa Medical Center, the county safety net hospital in Phoenix, Arizona serves a patient base which is 34.5% non-English speaking. The majority of these patients are uninsured or underinsured. A total of 1635 breast cancer patients were seen at least once at the Breast Clinic from June 1, 2006 to December 31, 2018. Sociodemographic variables were collected on all patients. All patients who were treated for breast cancer and then presented with a complaint of breast pain during follow up were evaluated. Additionally, all patients who complained of a breast mass but were found to have pain with no mass were evaluated in a similar fashion. Results: A total of 1577 patients were seen during the time period. The mean age of the patients was age 52. Of the patients, 144 presented with or developed metastatic disease prior to their operation. 116 patients transferred their care to another facility. Of the remaining patients, 36% of patients (474 of 1317) presented with a complaint of breast pain during their follow up after breast cancer treatment. Of the patients with breast pain, 16 had an ipsilateral breast tumor recurrence or contralateral breast cancer diagnosis, however, none of the patients presented with breast pain. The breast pain occurred after treatment was completed. Nine patients presented with a palpable mass and seven patients presented with abnormal imaging. In contrast, 6.0% patients (51 of 843) without breast pain developed an ipsilateral breast tumor recurrence, chest wall recurrence, or contralateral breast cancer. 35 patients presented with a painless breast mass and the remaining 26 recurrences or contralateral breast cancer were found on routine imaging. Local recurrence or contralateral breast cancer were more common in patients without breast pain during follow up (p = 0.036). The two most common factors related to any breast cancer recurrence and death were noncompliance with recommended treatment and presentation with T4 (Stage 3B) breast cancer. Conclusions: Mastalgia is a very common complaint in patients seen for follow up after breast cancer treatment. Patients and providers may believe a complaint of breast pain warrants further workup and often results in additional, repeat, or interval imaging. With normal physical examination and routine imaging, however, breast pain alone does not appear to be an indication of breast cancer recurrence. Additional or repeat imaging as well as laboratory tests do not appear beneficial in patients with breast pain. Reassurance and patient education is necessary to avoid continued use of unnecessary medical resources. Citation Format: Ian Komenaka, Anushi Shah, Tina Wong, Daniela Cocco, Chiu-Hsieh Hsu, Jesse Nodora, Waqas Arslan, Maria Elena Martinez. Breast pain is a common complaint after breast cancer treatment but not a sign of recurrence [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 P1-17-10.

Mortality after contralateral breast cancer in Denmark.

How a second breast cancer diagnosis affects survival in comparison with unilateral breast cancer (UBC) is unclear. Prognostic factors for contralateral breast cancer (CBC) are also not well established. We aimed to investigate the survival pattern after CBC with particular focus on time between first and second breast cancer diagnosis and age at CBC diagnosis. Within the nationwide Danish Breast Cancer Cooperative Group database, we identified 68,466 breast cancer patients diagnosed during 1978-2012. Patients who subsequently developed CBC were identified in a previously established database (N = 3004). Patients were followed for breast cancer-specific death in the Danish Register of Causes of Death until 2015. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazard regression models. Cumulative breast cancer mortality from date of CBC was estimated using the Aalen-Johansen method. Compared with UBC patients, the rate of dying from breast cancer was more than twofold higher following a CBC diagnosis, after adjustment for age, period, tumor characteristics, and treatment of the first breast cancer (HR 2.48; 95% CI 2.31-2.66). Short time interval (< 5years) was associated with higher breast cancer-specific mortality after CBC among patients < 70years at CBC diagnosis compared with longer time intervals, but not among patients ≥ 70years at CBC diagnosis. Breast cancer-specific mortality rates were markedly higher after compared with before a CBC diagnosis. We found higher breast cancer-specific mortality after CBC associated with a short interval between diagnoses among patients diagnosed with CBC before age 70years.

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.

Breast MRI increases the number of mastectomies for ductal cancers, but decreases them for lobular cancers

PurposeIn this retrospective population-based cohort study, we analyzed breast MRI use and its impact on type of surgery, surgical margin involvement, and the diagnosis of contralateral breast cancer.MethodsAll Dutch patients with cT1–4N0–3M0 breast cancer diagnosed in 2011–2013 and treated with primary surgery were eligible for inclusion. Using multivariable analyses, we analyzed in different categories whether MRI use was related to surgery type, margin involvement, and diagnosis of contralateral breast cancer (CBC).ResultsMRI was performed in 10,740 out of 36,050 patients (29.8%). Patients with invasive ductal cancer undergoing MRI were more likely to undergo primary mastectomy than those without MRI (OR 1.30, 95% confidence interval (CI) 1.22–1.39, p < 0.0001). Patients with invasive lobular cancer undergoing MRI were less likely to undergo primary mastectomy than those without MRI (OR 0.86, 95% CI 0.76–0.99, p = 0.0303). A significantly lower risk of positive surgical margins after breast-conserving surgery was only seen in patients with lobular cancer who had undergone MRI as compared to those without MRI (OR 0.59, 95% CI 0.44–0.79, p = 0.0003) and, consequently, a lower risk of secondary mastectomy (OR 0.61, 95% CI 0.42–0.88, p = 0.0088). Patients who underwent MRI were almost four times more likely to be diagnosed with CBC (OR 3.55, 95% CI 3.01–4.17, p < 0.0001).ConclusionsBreast MRI use was associated with a reduced number of mastectomies and less positive surgical margins in invasive lobular cancer, but with an increased number of mastectomies in ductal cancers. Breast MRI use was associated with a fourfold higher incidence of CBC.

Association of Adjuvant Tamoxifen and Aromatase Inhibitor Therapy With Contralateral Breast Cancer Risk Among US Women With Breast Cancer in a General Community Setting

Within 10 years after breast cancer diagnosis, roughly 5% of patients develop contralateral breast cancer (CBC). Randomized trials have found that therapy including tamoxifen citrate and aromatase inhibitors (AIs) reduces CBC risk. But little is known about the magnitude and duration of protective associations within the context of real-world clinical management settings, where varying durations of and gaps in treatment are common. To determine the association between adjuvant tamoxifen and AI therapy and CBC risk within a general community setting. A retrospective cohort study of CBC risk among 7541 patients diagnosed with a first primary unilateral invasive breast cancer at Kaiser Permanente Institute for Health Research (Colorado) or Kaiser Permanente Northwest Center for Health Research (Oregon) between January 1, 1990, and December 31, 2008. Data were analyzed from 1 year after diagnosis of the first breast cancer through the earliest of the following events: CBC diagnosis, other second cancer diagnosis, death, last tumor registry follow-up, exit from the Kaiser Permanente health care plan, or end of study follow-up (December 31, 2010, for Oregon and December 31, 2011, for Colorado). Adjuvant tamoxifen use and AI therapy were treated as time-dependent exposures, assessed using electronic prescription records. Incident CBC based on long-term systematic follow-up. Among 7541 women with invasive breast cancer, median age at initial breast cancer diagnosis was 60.6 years (age range, 24.9-84.9 years). Women were predominantly (92.9% [7009 of 7541]) of white race. During a median of 6.3 years (range, 1-20.9 years) of follow-up, 248 women developed CBC (45 in situ and 203 invasive). Contralateral breast cancer risk decreased significantly with increasing tamoxifen therapy duration. In current users, the relative risk (RR) per year of tamoxifen use was 0.76 (95% CI, 0.64-0.89), with an estimated 66% (RR, 0.34; 95% CI, 0.29-0.40) RR reduction for 4 years of use compared with nonusers. Risk reductions were slightly smaller for past users but were still significant at least 5 years after stopping tamoxifen therapy (RR per year of use, 0.85; 95% CI, 0.71-0.995). In addition, AI use without tamoxifen therapy was associated with reduced CBC risk (RR for AI users compared with nonusers, 0.48; 95% CI, 0.22-0.97). Risk reductions were most apparent among women whose primary and CBCs were estrogen receptor positive. Tamoxifen therapy was associated with reduced CBC risk during treatment and after its cessation, with risk progressively decreasing as tamoxifen therapy duration increased. Among those surviving at least 5 years, tamoxifen use for at least 4 years was estimated to prevent 3 CBCs per 100 women by 10 years after an estrogen receptor-positive first breast cancer, an absolute risk reduction that is consistent with findings from clinical trials. If adjuvant endocrine therapy is indicated for breast cancer treatment, these findings in concert with trial data suggest that women should be encouraged to complete the full course.

Contralateral breast cancer can represent a metastatic spread of the first primary tumor: determination of clonal relationship between contralateral breast cancers using next-generation whole genome sequencing.

IntroductionBy convention, a contralateral breast cancer (CBC) is treated as a new primary tumor, independent of the first cancer (BC1). Although there have been indications that the second tumor (BC2) sometimes may represent a metastatic spread of BC1, this has never been conclusively shown. We sought to apply next-generation sequencing to determine a “genetic barcode” for each tumor and reveal the clonal relationship of CBCs.MethodsTen CBC patients with detailed clinical information and available fresh frozen tumor tissue were studied. Using low-coverage whole genome DNA-sequencing data for each tumor, chromosomal rearrangements were enumerated and copy number profiles were generated. Comparisons between tumors provided an estimate of clonal relatedness for tumor pairs within individual patients.ResultsBetween 15–256 rearrangements were detected in each tumor (median 87). For one patient, 76 % (68 out of 90) of the rearrangements were shared between BC1 and BC2, highly consistent with what has been seen for true primary-metastasis pairs (>50 %) and thus confirming a common clonal origin of the two tumors. For most of the remaining cases, BC1 and BC2 had similarly low overlap as unmatched randomized pairs of tumors from different individuals, suggesting the CBC to represent a new independent primary tumor.ConclusionUsing rearrangement fingerprinting, we show for the first time with certainty that a contralateral BC2 can represent a metastatic spread of BC1. Given the poor prognosis of a generalized disease compared to a new primary tumor, these women need to be identified at diagnosis of CBC for appropriate determination of treatment. Our approach generates a promising new method to assess clonal relationship between tumors. Additional studies are required to confirm the frequency of CBCs representing metastatic events.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-015-0608-x) contains supplementary material, which is available to authorized users.

Prognosis, stage and oestrogen receptor status of contralateral breast cancer in relation to characteristics of the first tumour, prior endocrine treatment and radiotherapy

AimA contralateral breast cancer (CBC) is today treated as an independent primary tumour, although recent data suggest risk and prognosis of CBC to be influenced by characteristics of and treatment given for the first tumour (BC1). We hereby investigate phenotypical and prognostic features of the second tumour (BC2) in relation to prior endocrine treatment and radiotherapy. MethodsFrom a well-defined population-based cohort of CBC-patients, we have constructed a unique tissue-microarray including 600 pairs of primary tumours and CBCs. Breast cancer mortality was primary end-point for prognosis. ResultsBoth oestrogen receptor (ER) status and stage was strongly correlated between BC1 and BC2 within CBC-pairs. Although BC2 had the highest prognostic impact, BC1 continued to influence prognosis after diagnosis of CBC. Patients diagnosed with two high stage tumours within a short time-interval had a particularly bad prognosis. Prior endocrine therapy and radiotherapy both correlated to ER-negativity of BC2. An ER-negative BC2 was associated with an inferior prognosis compared to an ER-positive BC2 regardless of ER-status of BC1 or prior endocrine therapy. ConclusionsOur results suggest that both the residual prognostic impact of BC1, the possibility of contralateral metastasis, as well as prior treatment given, need to be considered when determining appropriate diagnostic work-up and treatment of CBC. In addition, radiation to the contralateral breast and risk of inducing CBC with an aggressive ER-negative phenotype should be considered when establishing new radiation treatment techniques. This study indicates loss of ER-expression as an important ‘endocrine treatment escape mechanism’, although further studies are warranted.

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.

Inferior survival for young patients with contralateral compared to unilateral breast cancer: a nationwide population-based study in the Netherlands

To compare overall survival between women with unilateral breast cancer (UBC) and contralateral breast cancer (CBC). Women with UBC (N=182,562; 95%) and CBC (N=8,912; 5%) recorded in the Netherlands Cancer Registry between 1989 and 2008 were included and followed until 2010. We incorporated CBC as a time-dependent covariate to compute the overall mortality rate ratio between women with CBC and UBC. Prognostic factors for overall death were examined according to age at first breast cancer. Women with CBC exhibited a 30% increase in overall mortality (Hazard Ratio (HR), 95% Confidence Interval: 1.3, 1.3-1.4) compared with UBC, decreasing with rising age at diagnosis of first breast cancer (<50years: 2.3, 2.2-2.5 vs. ≥70years: 1.1, 1.0-1.1). Women older than 50years at CBC diagnosis and diagnosed 2-5years after their first breast cancer exhibited a 20% higher death risk (1.2, 1.0-1.3) compared to those diagnosed within the first 2years. In women younger than 50years, the HR was significantly lower if the CBC was diagnosed >5years after the first breast cancer (0.7, 0.5-0.9). The prognosis for women with CBC significantly improved over time (2004-2008: 0.6, 0.5-0.7 vs. 1989-1993). Women with CBC had a lower survival compared to women with UBC, especially those younger than 50years at first breast cancer diagnosis. A tailored follow-up strategy beyond current recommendations is needed for these patients who, because of their age and absence of known familial risk, are currently not invited for population-based screening.

Body mass index and risk of second primary breast cancer: The WECARE Study

The identification of potentially modifiable risk factors, such as body size, could allow for interventions that could help reduce the burden of contralateral breast cancer (CBC) among breast cancer survivors. Studies examining the relationship between body mass index (BMI) and CBC have yielded mixed results. From the population-based, case-control, Women's Environmental, Cancer and Radiation Epidemiology (WECARE) Study, we included 511 women with CBC (cases) and 999 women with unilateral breast cancer (controls) who had never used postmenopausal hormone therapy. Rate ratios (RR) and 95% confidence intervals (CI) were used to assess the relationship between BMI and CBC risk. No associations between BMI at first diagnosis or weight-change between first diagnosis and date of CBC diagnosis (or corresponding date in matched controls) and CBC risk were seen. However, obese (BMI ≥ 30 kg/m(2)) postmenopausal women with estrogen receptor (ER)-negative first primary tumors (n = 12 cases and 9 controls) were at an increased risk of CBC compared with normal weight women (BMI < 25 kg/m(2)) (n = 43 cases and 98 controls) (RR = 5.64 (95% CI 1.76, 18.1)). No association between BMI and CBC risk was seen in premenopausal or postmenopausal women with ER-positive first primaries. Overall, BMI is not associated with CBC risk in this population of young breast cancer survivors. Our finding of an over five-fold higher risk of CBC in a small subgroup of obese postmenopausal women with an ER-negative first primary breast cancer is based on limited numbers and requires confirmation in a larger study.

Abstract P4-09-07: Prediction of Outcome after Diagnosis of Metachronous Contralateral Breast Cancer

Abstract Background: Contralateral breast cancer (CBC) is today treated as a new primary tumour, but the biological relationship between the first (BC1) and the second breast cancer (BC2), and the impact of a second primary tumour on prognosis is debated. Using a unique patient cohort, we have investigated whether time interval to BC2 and mode of detection are associated to prognosis. Methods: For all patients diagnosed with metachronous CBC in the Southern Healthcare Region of Sweden from 1977-2007, information on patient, tumour, treatment characteristics, and outcome was abstracted from patients’ individual charts. The final cohort included 724 patients with metachronous CBC as primary event. Primary endpoint was distant disease-free survival (DDFS), which was measured from diagnosis of CBC. To avoid lead-time bias, we looked at risk of metastasis or breast cancer death as a primary event instead of DDFS in relation to mode of detection. Metachronous breast cancer was defined as CBC diagnosed at least three months after BC1. Age refers to age at BC1. Results: Patients with a time interval to BC2 of less than three years had a significantly impaired DDFS (HR=1.4, p=0.01). Significance remained in multivariate analysis adjusted for age, calendar period, mode of detection of BC2, size, lymph node status, and treatment for BC 1 and BC2 (HR= 1.6, p=0.01). Subgroup analysis showed this effect to be seen primarily in patients aged &amp;lt;50. Using an interaction analysis between age and time interval to BC2, the interaction was statistically significant in univariate (HR=0.53, p=0.03), but not in multivariate analysis. Patients diagnosed with CBC within a follow-up programme were considered asymptomatic at diagnosis (63%), while patients who first noted symptoms themselves were considered symptomatic (37%). Patients with symptoms at diagnosis were younger, had a longer time interval to BC2, had larger CBCs, and more often lymph node metastases. Using logistic regression, a significantly higher risk of later developing metastases was seen in symptomatic patients, both in univariate (HR=2.1, P&amp;lt;0.0001) and multivariate analysis (HR=2.1, p=0.002). When exploring effect of mode of detection in relation to time interval to BC2, mode of detection remained a significant prognostic factor even when time interval to BC2 was more than ten years. Discussion: Why CBC diagnosed within a short time interval from BC1 seems to have a worse prognosis is unclear. One explanation could bethat these tumours more often represent a metastatic spread of BC1, another that CBC diagnosed during or soon after adjuvant treatment has developed treatment resistance and a more aggressive phenotype. Mode of detection was associated with risk of metastasis even when BC2 was diagnosed more than ten years after BC 1, suggesting that a long follow-up time could be of value. Conclusion: In a large cohort of patients with CBC, we found time interval to BC2 and mode of detection to be strong prognostic factors. CBC is today treated as a new primary tumour. The prognostic factors found in the present study could be of value in identifying patients needing intensified treatment. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-09-07.

Local Therapy in BRCA1/2 Carriers with Operable Breast Cancer: Comparison of Breast Conservation and Mastectomy.

Abstract Background: Women with inherited germline BRCA1/2 mutations have a 55-85% cumulative risk of breast cancer (BC) by age 70. Thus, knowledge of expected outcomes following various treatments is needed to advise these patients should they be diagnosed with BC. It is unclear whether breast conservation (BCT) offers similar rates of tumor control as mastectomy (M) in BRCA1/2 carriers and it is doubtful whether a randomized trial comparing these options could be performed. Thus, this analysis compares the outcomes between similarly staged women with BRCA1/2 mutations treated with BCT vs. M.Methods: Women with deleterious BRCA1/2 mutations diagnosed with operable BC and who consented to longitudinal studies were identified at 10 institutions in the US, Australia, Spain and Israel. Patient, clinical and treatment characteristics were compared between those receiving BCT and those receiving M +/- RT. Time-to-event endpoints included first failure of treatment, diagnosis of contralateral breast cancer (CBC), and overall and BC-specific survival. Cox regression models were constructed to detect significant associations between patient and clinical characteristics and time-to-event endpoints.Results: Clinical characteristics and outcomes for 302 BCT and 353 M patients were compared. With a median F/U of 8.2 years for BCT patients and 8.9 years following M, 15-year local failure as first failure was significantly higher with BCT vs. M (23.5% vs. 5.5%, p&amp;lt;0.0001). Multivariate analysis indicted choice of local therapy as the only factor significantly predicting local recurrence, with a 4.5-fold risk of local failure with BCT compared to M (p&amp;lt;0.0001). Local failure analyses by cohort revealed the presence of a BRCA2 mutation (HR 2.8; p=0.024) and no use of adjuvant chemotherapy (HR 5.4; p=0.0001) as significant predictors within the BCT group; presence of invasive lobular cancer (HR 9.9; p=0.004) was the only significant predictor within the M cohort. No significant differences were seen in distant failure, BC-specific or overall survival by local therapy. 15-year estimates of CBC were 52.1% with BCT; 41.4% with M; and 37.9% with M+RT (p=0.44). Analyses of BCT vs. M +/- RT and surgery +/- RT did not reveal significant differences in CBC by cohort.Conclusions: The higher risk of local failure in BRCA1/2-associated BC treated with BCT compared to M did not translate into an increased risk of distant failure or mortality. RT did not result in a detectable increase in CBC at 15 years above baseline elevated rates. These results at both the involved and contralateral breasts should be discussed when patients with BRCA1/2-associated BC are considering local treatment options. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 959.

Contralateral breast cancer: factors associated with stage and size at presentation.

Few reports have evaluated factors associated with the stage at presentation of contralateral breast cancer and whether contralateral cancer presentation has changed in recent years, during which increased screening and enhanced adjuvant therapy of the initial tumor has been introduced. Patients with initial cancers staged 0-IIIB diagnosed between 1980 and 1999 who subsequently developed contralateral breast cancer were evaluated for stage, primary tumor size and histologic features, patient age and year of diagnosis, synchronous or metachronous presentation, and time from initial tumor to diagnosis of contralateral breast cancer. Tumor presentation was compared with contemporaneously diagnosed unilateral breast cancer patients. A total of 171 patients were diagnosed with contralateral breast cancer; 161 cases if lobular carcinoma in situ for either the initial or the contralateral tumor were excluded. Contralateral tumors were of significantly smaller size and of earlier stage than initial tumors. Contralateral cancers demonstrated earlier stage distributions with more recent year of diagnosis; initial tumors in contralateral patients did not. Earlier stage at presentation of contralateral tumors was associated in a multivariate model with more recent year of contralateral tumor diagnosis and earlier stage at presentation of the initial tumor; contralateral tumor size was associated with the size of the initial tumor. More recently diagnosed contralateral breast cancers are presenting with earlier stages of disease. The stages of initial tumors in these patients have not undergone such an improvement. Initial tumor size and stage is strongly associated with contralateral breast cancer size and stage; this association is independent of the year of diagnosis. Increased compliance with screening might be expected to improve both initial tumor stage and tumor size presentations in contralateral tumor patients, as well as the presentation of contralateral cancers.

The influence of tamoxifen treatment on the oestrogen receptor in metachronous contralateral breast cancer

Adjuvant tamoxifen treatment reduces the occurrence of contralateral breast cancer (CBC). The aim of the study was to investigate the hypothesis that adjuvant tamoxifen reduces the occurrence of oestrogen-receptor (ER)-positive CBC, but not the growth of ER-negative CBCs, and to examine survival after diagnosis of CBC. For the study, ER status was immunohistochemically assessed in CBCs of 35 tamoxifen-treated patients and 115 patients without previous hormonal treatment. Cases were retrieved from a series of patients treated from 1984 to 1995 at nine hospitals. The interval between ipsi- and contralateral breast cancer was at least 1 year. It was seen that the proportion of patients with an ER-negative CBC was significantly higher among those with prior tamoxifen treatment: 37% vs 18% (P=0.047). No difference between the two groups in overall and disease-specific survival following CBC was found. However, the stage differed for both groups: tamoxifen users more often had node-positive contralateral disease (P= 0.045). In conclusion, metachronous CBCs developing after 1–3 years of tamoxifen treatment are more often ER-negative breast cancers. So far this does not seem to have a major impact on survival.