Contralateral Breast Cancer Recurrence Research Articles

Abstract PS06-06: Analysis of ctDNA for the detection of minimal residual disease (MRD) using a tissue-free, multiomic assay in patients with early-stage breast cancer

Abstract Background: The detection of ctDNA in patients with early-stage breast cancer after completion of adjuvant therapy is associated with a high risk of recurrence. Current clinical guidelines do not recommend routine screening for metastatic disease unless there are clinical signs and symptoms in patients who completed adjuvant therapy. However, ctDNA may serve as an early biomarker of recurrence which may allow effective identification of patients with asymptomatic distant metastases or molecular relapse only, who could benefit from early treatment intervention. Herein, we utilized a tissue-free, multiomic assay for the sensitive and specific detection of MRD in patients with early-stage breast cancer. Methods: Plasma samples were collected from patients with stage I-III breast cancer who were enrolled in the SUCCESS-A phase 3 clinical trial (NCT02181101) between 2006 and 2007. All patients received adjuvant chemotherapy +/- endocrine therapy and/or anti-HER2 therapy. Samples were collected approximately two years after completion of adjuvant chemotherapy, and plasma samples selected for analysis were from patients without evidence of disease recurrence prior to sample collection. Presence of MRD was assessed using Guardant Reveal powered by Infinity, which evaluates the epigenomic signals associated with cancer versus normal DNA for the detection of ctDNA. Samples with the presence of ctDNA are characterized for somatic alterations with common sources of interference such as clonal hematopoiesis excluded. An analytically validated bioinformatics pipeline was used for the detection of breast cancer ctDNA. Samples were analyzed blinded to the clinical data. Median survival times were estimated using the Kaplan-Meier method and hazard ratios were calculated based on univariable cox regression models. Results: A total of 311 plasma samples from 311 patients were evaluable. ctDNA was detected in 34% (13/38) of patients who subsequently developed distant recurrence and in none (0/7) of the patients who had local or contralateral breast cancer recurrence. ctDNA was detected in 60% (9/15) of samples that were collected within one year before recurrence. In the ctDNA detected samples from patients who had disease recurrence, the median time from sample collection to recurrence was 7.9 months (range, 1.4-28.6 months). ctDNA was detected in 6 patients who did not have a documented disease recurrence, resulting in a specificity of 97.7% (260/266). In the overall cohort, ctDNA detection was prognostic for recurrence-free survival (RFS; HR 11.0, 95% CI 2.28-53.6; p< 0.0001), distant recurrence-free survival (D-RFS; HR 13.7, 95% CI 2.52-74.9; p< 0.0001), and overall survival (OS; HR 17.4, 95% CI 1.33-227; p< 0.0001). Conclusion: Detection of ctDNA after adjuvant chemotherapy was highly prognostic and demonstrated high specificity in an early-stage breast cancer cohort. Larger, prospective studies are needed to confirm the prognostic value of ctDNA in the post-treatment setting and assess the clinical utility of MRD detection in this population. Citation Format: Wolfgang Janni, Thomas Friedl, Brigitte Rack, Peter A. Fasching, Andreas Hartkopf, Hans Tesch, Ralf Lorenz, Georg Heinrich, Jens-Uwe Blohmer, Tanja Fehm, Volkmar Müller, Andreas Schneeweiss, Matthias Beckmann, Matthias Ruebner, Nadia Harbeck, Klaus Pantel, Derek Dustin, Mingyang Cai. Analysis of ctDNA for the detection of minimal residual disease (MRD) using a tissue-free, multiomic assay in patients with early-stage breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS06-06.

Long-term oncologic outcomes of unselected triple-negative breast cancer patients according to BRCA1/2 mutations

Triple-negative breast cancer (TNBC) patients are more likely to have BRCA1/2 mutations, with a prevalence rate of about 10–20%. Although several studies have analyzed the oncologic outcomes between BRCA1/2 carriers and non-carriers, the impact on breast cancer patients is still unclear. A retrospective review was performed to determine the long-term outcomes of TNBC patients, focusing on the impact of BRCA1/2 mutations. A total of 953 TNBC patients who underwent primary breast cancer surgery from June 2008 to January 2016 were included. We examined long-term outcomes, including contralateral breast cancer (CBC) incidence, recurrence patterns, and survival rates over a median follow-up of 80.9 months (range 3–152 months). 122 patients (12.8%) had BRCA1/2 mutations. BRCA1/2 mutation carriers were significantly younger at diagnosis and more likely to have a family history of breast/ovarian cancer. CBC incidence at 60, 120, and 150 months was significantly higher in BRCA1/2 mutation carriers compared to non-carriers (P = 0.0250, 0.0063, and 0.0184, respectively). However, there were no significant differences in disease-free survival, overall survival, breast cancer-specific survival, or distant-metastasis-free survival between the two groups. BRCA1/2 mutation status was a significant risk factor for CBC (HR = 6.242, P < 0.0001). Interestingly, among 29 patients with CBC recurrence, 24 patients (82.8%) had recurring TNBC subtype and among the CBC recurrence patients, 19 patients (65.5%) resumed chemotherapy. In the TNBC subtype, appropriate genetic testing and counseling are pivotal for surgical decisions like risk-reducing mastectomy (RRM). Furthermore, long-term surveillance is warranted, especially in BRCA1/2 carriers who did not receive RRM.

Increased risk of contralateral breast cancer for BRCA1/2 wild-type, high-risk Korean breast cancer patients: a retrospective cohort study

BackgroundThis study aimed to investigate the contralateral breast cancer (CBC) recurrence rate in Korean breast cancer patients according to their BRCA1/2 germline mutation status, focusing particularly on the CBC recurrence risk in BRCA1/2 negative (BRCAx) patients.MethodsWe conducted a retrospective study on 13,107 primary breast cancer patients. The patients were divided into high-risk and low-risk groups for hereditary breast cancer based on the Korean National Health Insurance Service’s eligibility criteria for BRCA1/2 germline mutation testing. The high-risk group was further categorized into the BRCAmutation group, the BRCAxgroup, and the not tested group. We evaluated the overall survival and cumulative risk of developing CBC in these patients.ResultsAmong 4494 high-risk patients, 973 (21.7%) underwent genetic testing for BRCA1/2 germline mutation, revealing mutations in 158 patients (16.2%). We observed significant overall survival differences across all four groups, with the high-risk, not-tested group demonstrating notably worse overall survival (p < 0.001). However, when adjusted for other prognostic factors, there was no significant differences in hazard ratio of death between the four groups. The cumulative risk of CBC also varied among the groups. Patients with BRCA1/2 mutations showed a 7.3-fold increased risk of CBC compared to the low-risk group (95% CI 4.11–13.0, p < 0.001). Interestingly, BRCAx patients also demonstrated a significantly higher risk of CBC (HR 2.77, 95% CI 1.76–4.35, p < 0.001). The prognostic importance of the BRCAx for CBC recurrence persisted after adjusting for the age and subtype, but became insignificant when the family history of breast cancer was adjusted.ConclusionBreast cancer patients who are at high risk of hereditary breast cancer but with wild-type BRCA 1/2 genes (BRCAx) have increased risk of developing contralateral breast cancer when compared to the low-risk patients. More careful surveillance and follow-up can be offered to these patients especially when they have family history of breast cancer.

Abstract P5-03-01: Long-term oncologic outcome of unselected triple-negative breast cancer patients according to BRCA1/2 mutations: a comprehensive single institution study

Abstract Background Triple-negative breast cancer (TNBC) is known to have a higher risk of early recurrence and relatively low risk of late recurrence compared to luminal type breast cancer. Among all subtypes of breast cancer, TNBC is more likely to have BRCA1/2 germline mutation which showed prevalence rate from about 10% to 20% in previous reports. To date, there are only few studies about the effect of BRCA1/2 mutations on the long-term oncologic prognosis in TNBC patients. We analyzed long-term oncologic outcome in unselected TNBC patients according to BRCA1/2 mutations in a comprehensive single institution. Methods Among 11,994 patients who underwent primary breast cancer surgery at Samsung Medical Center (SMC) between June 2008 and January 2016, 1,628 (13.6%) were TNBC patients. Of those, patients with inadequate and unavailable samples at SMC biobank and patients with follow-up duration less than 12 months and who had distant metastasis at presentation were excluded from the study, and 953 patients were enrolled. A retrospective study was conducted and BRCA1/2 genetic testing was done with SMC biobank samples through Next Generation Sequencing (NGS). Results Among 953 unselected TNBC patients, 122 patients (12.8%) had BRCA1/2 mutations: 91 (9.5%) were in BRCA1, and 32 (3.4%) were in BRCA2. One patient had both BRCA1/2 mutations. BRCA1/2 carriers were more likely to have personal history of ovarian cancer (9.0% vs. 0.5%, p &amp;lt; 0.0001), family history of breast cancer and/or ovarian cancer (40.2% vs. 9.4%, p &amp;lt; 0.0001), bilateral breast cancer (4.9% vs. 1.2%, p = 0.0105), and higher nuclear grade (86.0% vs. 74.0%, p = 0.0250). The median follow-up duration was 80.9 months. There were no significant differences in disease-free survival (DFS), distant metastasis-free survival (DMFS), overall survival (OS), and breast cancer-specific survival (BCSS) (p = 0.375, 0.268, 0.413, and 0.133, respectively) between BRCA1/2 carriers and non-carriers. However, BRCA1/2 carriers showed significantly worse contralateral breast cancer (CBC)-free survival than non-carriers (p &amp;lt; 0.0001). Sixty and 120-months cumulative recurrence rate were 18.5% and 31.2% for BRCA1/2 carriers versus 19.3% and 22.7% for non-carriers (p = 0.834 and 0.136, respectively). However, cumulative recurrence rate at 150 months showed absolute but not statistically significant difference between BRCA1/2 carriers and non-carriers (36.2% versus 23.5%, p = 0.080). Cumulative CBC recurrence rate on 60, 120- and 150-months estimates were 6.7%, 18.7% and 25.5% for BRCA1/2 carriers versus 1.1%, 2.7% and 5.2% for non-carriers which showed statistically meaningful difference (p = 0.025, 0.006 and 0.018, respectively). Sixty months, 120- and 150-months cumulative expire rate were 11.2%, 15.6% and 27.7% for BRCA1/2 carriers versus 14.3%, 20.7% and 20.7% for non-carriers (p = 0.319, 0.202 and 0.549, respectively). Discussion In this unselected cohort of patients with TNBC, we found 12.8% (122 patients among 953) prevalence of BRCA1/2 mutations. The median follow-up duration was 80.9 months. There was no significant difference in DFS, DMFS, OS and BCSS by BRCA1/2 mutation status in long-term follow up. However, BRCA1/2 carriers showed significantly worse CBC recurrence rate at 60, 120- and 150- months. And also, BRCA1/2 carriers had 12.7% higher risk of recurrence than non-carriers at 150 months, which was not statistically meaningful but showed absolute difference. Among patients with CBC recurrence, 41.3% (12 patients among 29) were BRCA1 carriers, over 85% had TNBC type of recurred CBC and approximately 80% underwent chemotherapy. In conclusion, we demonstrated that CBC recurrence risk is relatively high in TNBC patients with BRCA1 mutation and showed high chance to receive chemotherapy. Therefore, long-term follow up and appropriate genetic counseling, risk assessment should be done properly for BRCA1/2 mutation carriers in TNBC patients. Citation Format: Soo Yeon Chung, Jai Min Ryu, You Jin Jung, Yeon Jin Kim, Hye Jin Kim, Seok Jin Nam, Seok Won Kim, Jonghan Yu, Byung Joo Chae, Jeong Eon Lee, Se Kyung Lee, Sung-Won Kim, Eun Young Kim. Long-term oncologic outcome of unselected triple-negative breast cancer patients according to BRCA1/2 mutations: a comprehensive single institution study [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 P5-03-01.

Extended Adjuvant Therapy With Aromatase Inhibitors for Early Breast Cancer: A Meta-analysis of Randomized Controlled Trials

BackgroundAromatase inhibitors (AIs) are widely used for early breast cancer, whereas the efficacy and safety of extended AI adjuvant therapy compared with shorter AI therapy, observation, or placebo remains controversial. We conducted a quantitative meta-analysis to summarize available randomized controlled trials (RCTs) regarding the efficacy and safety of extended AI therapy for early breast cancer. Materials and MethodsWe systematically searched PubMed, EmBase, and the Cochrane library to select studies published through March 2018. Studies designed as RCTs and that investigated overall survival (OS) or disease-free survival (DFS) for extended AI and shorter AI therapy, observation, or placebo were included. Hazard ratio (HR) and relative risk (RR) with 95% confidence intervals (CIs) were employed to pool analysis according to data type. ResultsWe identified 7 RCTs that involved 16,926 patients with early breast cancer. The summary HRs indicated that extended treatment with AIs was not associated with OS (HR, 0.95; 95% CI, 0.82-1.10; P = .488), whereas it could significantly improve DFS as compared with shorter AI therapy, observation, or placebo (HR, 0.75; 95% CI, 0.66-0.86; P < .001). Treatment with extended AIs significantly reduced contralateral breast cancer recurrence (RR, 0.46; 95% CI, 0.34-0.64; P < .001), whereas it has no significant effect on distant metastatic recurrence (RR, 0.80; 95% CI, 0.64-1.00; P = .055), and locoregional recurrence (RR, 0.76; 95% CI, 0.53-1.08; P = .127). There were no significant differences between treatment with extended AIs and control for grade 3 or more adverse events. ConclusionExtended AI therapy could significantly improve DFS, especially for contralateral breast cancer recurrence. There were no significant differences between treatment with AIs and control for OS, distant metastatic and locoregional recurrence, and serious adverse events.

50P - Contemporary risk of local, regional and contralateral breast cancer recurrence

Background: Follow-up of breast cancer patients aims to detect curable recurrence, and focuses on ipsilateral in-breast recurrence (LR), regional lymph node recurrence (RR) and contralateral breast cancer (CBC). The present study aimed to address contemporary loco-regional recurrence rates evaluating time trends and the role of contributing factors. Material and methods: The Netherlands Cancer Registry was searched for all female patients diagnosed and operated for a unilateral primary breast cancer (pT1-2, anyN, M0) between 2003 and 2006. The 5-year risk of developing LR, RR and CBC were estimated using Kaplan Meier curves. Prognostic influence of various patient- and disease characteristics was assessed. Results: A total of 35.006 eligible patients were identified. The 5-year rates of LR, RR, and CBC are presented in Table 1. The risk of CBC was higher than LR and RR. Over time, the rates decreased significantly for all three endpoints.Tabled 1Overall 5-year risk of local, regional and contralateral recurrence and distant metastases over time (period 2003-2006)Local recurrenceaLocal recurrence (ipsilateral in-breast recurrence + new primary) Rates represent Kaplan Meier estimates.Regional recurrenceContralateral breast cancerDistant metastasesno. of eventsrate (%)no. of eventsrate (%)no. of eventsrate (%)no. of eventsrate (%)2003 (n = 8.933)1852,4%861,1%2273,1%7899,8%2004 (n = 9.048)1812,4%831,1%1892,5%7839,6%2005 (n = 9.055)1441,8%750,9%1902,5%6928,5%2006 (n = 7.970)1311,9%500,7%1462,1%5617,7%Overall(n = 35.006)6412,1%2941,0%7522,6%2.8258,9%a Local recurrence (ipsilateral in-breast recurrence + new primary) Rates represent Kaplan Meier estimates. Open table in a new tab The LR-rate was lower with breast conserving surgery (BCS) vs. amputation (1.8% vs. 2.5%), T1a-b vs. T1c-T2 tumors (2.0% vs. 2.5%), ER+ vs. ER- tumors (1.8% vs. 3.5%) and inversely related with age (highest in pts. <35 yrs: 2.9%). The 5-year RR-rate was 0.9% for N0 patients, and decreased from 1.0% to 0.7% over time. The risk of RR after amputation decreased from 1.8% to 0.9% over time, but was higher than after BCS (1.6% vs. 0.6%). Overall, the RR-rate was highest in the N > 1 group (1.4%) and the triple negative group (2.0%). The CBC-rate was lower for patients who received chemotherapy (CT) than for patients who did not (1.6% vs. 3.1%). The CBC-rate only decreased over the years in the CT-group (3.7% to 2.5%). Conclusions: Loco-regional recurrence rates have decreased substantially in recent years and have become very low. For the vast majority of patients the risk of LR is substantially lower than the risk of CBC and the risk of RR is rarely larger than 1.0%. These low rates might reflect improvements in systemic treatment. Disclosure: All authors have declared no conflicts of interest.

Abstract P6-08-01: Contemporary risk of local, regional and contralateral breast cancer recurrence

Abstract Background Long-term follow-up of breast cancer patients aims to detect curable recurrence, and focuses on ipsilateral in-breast recurrence (LR), regional lymph node recurrence (RR) and contralateral breast cancer (CBC). In recent years there is mounting evidence of a decrease in locoregional recurrence rates. Non-surgical-treatment modalities have evolved extensively, while surgery has become less invasive over the last fifteen years. The present study aimed to address contemporary loco-regional recurrence rates evaluating time trends and the role of contributing factors. Material and methods The Netherlands Cancer Registry was searched for all female patients diagnosed and operated for a unilateral primary breast cancer (pT1-2,anyN,M0) between 1-1-2003 and 31-12-2006. Exclusion criteria were previous cancer, neo-adjuvant chemotherapy or incurable disease. Data on 5-year follow-up were available from hospital records and included the first site of recurrence and contralateral breast cancer (CBC). The 5-year risk of developing LR, RR and CBC were estimated using Kaplan Meier curves. Patients were censored at time of death, lost to follow-up or the development of distant metastases. Prognostic influence of various patient- and disease characteristics was assessed. Results A total of 35.006 eligible patients were identified. The 5-year rates of LR, RR, and CBC are presented in Table 1. The risk of CBC was higher than LR and RR. Over time, the rates decreased significantly for all three endpoints. Table 1. Overall 5-year risk of local, regional and contralateral recurrence and distant metastases over time (period 2003-2006) Local recurrence(a)Regional recurrenceContralateral breast cancer no. of eventsrate (%)no. of eventsrate (%)no. of eventsrate (%)2003 (n=8933)1852,40%861,11%2273,08%2004 (n=9048)1812,35%831,07%1892,51%2005 (n=9055)1441,84%750,95%1902,49%2006 (n=7970)1311,87%500,70%1462,05%Overall (n=35.006)6412,12%2940,96%7522,55%(a)Local recurrence (ipsilateral in-breast recurrence + new primary). Rates represent Kaplan Meier estimates The LR-rate was lower with breast conserving surgery (BCS) vs. amputation (1.8% vs. 2.5%), T1a-b vs. T1c-T2 tumors (2.0% vs. 2.5%), ER+ vs. ER- tumors (1.8% vs. 3.5%) and inversely related with age (highest in pts. &amp;lt;35 yrs: 2.9%). LR rate seemed independent of HER2 status. The 5-year RR-rate was 0.9% for N0 patients, and decreased from 1.0% to 0.7% over time. The risk of RR after amputation decreased from 1.8% to 0.9% over time, but was higher than after BCS (1.6% vs. 0.6%). Overall, the RR-rate was highest in the N&amp;gt;1 group (1.4%) and the triple negative group (2.0%). The CBC-rate was lower for patients who received chemotherapy (CT) than for patients who did not (1.6% vs. 3.1%). The CBC-rate only decreased over the years in the CT-group (3.7% to 2.5%). Conclusions Loco-regional recurrence rates have decreased substantially in recent years and have become very low. For the vast majority of patients the risk of LR is substantially lower than the risk of CBC and the risk of RR is rarely larger than 1.0%. These low rates might reflect improvements in systemic treatment. Citation Format: Kim C Aalders, Annelotte CM van Bommel, Thijs van Dalen, Gabe S Sonke, Paul J van Diest, Liesbeth J Boersma, Margriet van der Heiden-van der Loo. Contemporary risk of local, regional and contralateral breast cancer recurrence [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-08-01.

Incidence of contralateral breast cancer in Japanese patients with unilateral minimum-risk primary breast cancer, and the benefits of endocrine therapy and radiotherapy

Tamoxifen is recommended as adjuvant endocrine therapy for patients with minimum-risk breast cancer. It is primarily effective at prevention of contralateral and ipsilateral breast cancer recurrence after breast-conserving surgery. The incidence of contralateral breast cancer and the absolute benefit of endocrine therapy among patients with unilateral minimum-risk breast cancer in Japan, where the incidence of breast cancer is low, are unknown. We retrospectively studied the incidence of contralateral breast cancer, and the efficacy of endocrine therapy, in a cohort of 2074 Japanese women with unilateral breast cancer whose primary tumor was pTis (n=1905) or pT1mic (n=169) (unknown for endocrine therapy, n=4; unknown for radiotherapy, n=2). We also assessed the efficacy of endocrine therapy and radiotherapy for prevention of ipsilateral and contralateral breast cancer recurrence in 1205 patients who underwent breast-conserving surgery (unknown for endocrine therapy, n=2; unknown for radiotherapy, n=2). The incidence of contralateral breast cancer per 1000 person-years was 5.1 (95% confidence interval (CI), 3.7-7.1) among patients without endocrine therapy (n=1364) and 3.6 (95% CI 2.1-6.1) among those with endocrine therapy (n=706). The incidence of ipsilateral breast cancer recurrence after breast-conserving surgery per 1000 person-years was 9.2 (95% CI 6.5-13) among patients without endocrine therapy (n=753) and 4.2 (95% CI 2.2-8.1) among those with endocrine therapy (n=450). The incidence of ipsilateral breast cancer recurrence after breast-conserving surgery per 1000 person-years was 9.9 (95% CI 6.3-15.6) among patients without radiotherapy (n=380) and 5.9 (95% CI 3.9-9.0) among those with radiotherapy (n=823). The incidence of contralateral breast cancer among minimum-risk breast cancer patients in Japan, where the incidence of breast cancer is low, was similar to that in Western countries. Endocrine therapy is indicated for this population.

Obesity a significant risk factor for contralateral breast cancer ocurrence.

Abstract Abstract #6097 Background: The health consequences of obesity are significant and it's effect on breast cancer outcomes are now being recognized. Several risk factors for contralateral breast cancer recurrence included age, lobular histology, genetic abnormalities and no prior adjuvant systemic therapy. This study's objective was to define the risk of contralateral breast cancer in obese patients following treatment for primary breast cancer.&amp;#x2028; Methods: The electronic medical records of pts with histologically proven invasive breast cancer diagnosed between 1981 from 2006 were reviewed. Patients with Stage IV at diagnosis were excluded. Intrammamary breast cancer recurrence was defined as a new diagnosis of invasive or in-situ breast cancer at least 6 months after the diagnosis of primary invasive breast cancer, and it was classified as ipsilateral or contralateral breast cancer. Data on insurance, race, body mass index at diagnosis (BMI) and disease free interval (DFI) was analyzed. National Institutes of Health criteria was used to stratify pts as obese (BMI &amp;gt;30 kg/m2). Differences in DFI were analyzed by BMI.&amp;#x2028; Results: Of the 647 pts who were diagnosed with invasive breast cancer, 72 pts (11%) had intrammamary breast cancer recurrence, (28 ipsilateral and 44 contralateral). Pts with contralateral breast cancer in comparison with pts with ipsilateral breast cancer were more likely to be obese at diagnosis (64% vs 25%; p=0.001), to have a higher mean age at diagnosis (51 years vs 46 years; p=0.04) and to have primary breast cancer with ER positive status (67% vs 39%; p=0.05). In univariate analysis, obesity is a significant predictor of contralateral breast cancer. (HR =1.97; p=0.04). In multivariate analysis using Cox regression model, after adjusting for race, menopausal status, stage and SES, age at diagnosis and BMI remain statistically significant predictors for contralateral breast cancer (age at diagnosis: HR=1.09; p=0.006; BMI: HR=4.9; p=0.004).&amp;#x2028; Conclusions: In this relatively small patient group, obesity represent a significant risk factor for contralateral breast cancer occurrence. Additional studies are needed to further define the impact of obesity in breast cancer outcomes. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6097.

Prophylactic mastectomy

Women with increased risk of breast cancer have the treatment options of chemoprevention, surveillance or prophylactic mastectomy (PM). This article will focus on PM. PM should only be undergone after a detailed risk assessment and consultation with the patient's entire medical team, including a psychologist. PM will either be bilateral or contralateral. Bilateral PM is usually recommended to women who have a genetic predisposition for breast cancer. Research has shown that PM was 98.6% effective in preventing breast cancer in BRCA1 or BRCA2 mutation carriers. Contralateral PM (CPM) is a treatment option not often recommended to women who are being treated for breast cancer. While research has shown that CPM can offer a 95% risk reduction to contralateral breast cancer recurrence, the low risk of developing a contralateral breast cancer in the first place (0.6%) means that CPM would actually offer little benefit to most patients. However, it should be noted that the efficacy of PM for patients with invasive lobular carcinoma is controversial and further research is needed. The optimal surgical technique for removing the most breast tissue is total mastectomy, while new techniques of ‘skin sparing’ mastectomy will allow a better cosmetic outcome following reconstruction.

A parametric regression model of tumor recurrence: An application to the analysis of clinical data on breast cancer

A new parametric model is proposed for the regression analysis of relapse-free time data. It offers a natural classification of covariates in terms of their predominant effect either on the expected number of clonogens in a treated tumor or on the time of tumor progression. Within the framework of the model, the probability of local control is uniquely determined by the mean number of surviving clonogenic cells. Two versions of the model are considered; in one of them every mode of treatment is represented by indicator variables while in the other version the linear-quadratic model of radiation cell survival is used to describe the effect of radiotherapy. Maximum likelihood estimation of the model parameters is provided by a nonlinear programming procedure which has been shown to be computationally tractable. The results are reported of the analysis of relevant data on breast cancer recurrence after conservative treatment of the primary tumor. The most striking finding is that age of a patient exerts a very strong effect on the mean number of surviving clonogens in the ipsilateral breast, or equivalently, the probability of tumor cure, while its effect on the progression time appears to be negligible. On the other hand, the primary tumor size contributes significantly to both characteristics of tumor latency. No significant covariate effects emerged from the analysis of the contralateral breast cancer recurrence.

Testing the Independence of Competing Risks: An Application to the Analysis of Breast Cancer Recurrence

AbstractAs evidenced by the results of data analysis the contralateral breast cancer recurrence is most likely to originate from subclinical tumor foci that preexist at the time of treatment This raises the natural question as to whether the rtcumnas in the contralateral breast evolve independently of those in the ipsilateral breast It is common knowledge in the theory of competing risks that this problem can not be solved within the nonparaoretric framework. To overcome the obstacle om needs to proceed from a biologically‐based parametric model of tumor latency. We explore this possibility with a model proposed earlier (HOANG et al., 1992). When incorporated into a family of joint distributions with given marginal distributions for the tumor latency times, the model allows testing the independencc hypothesis by the likelihood ratio test Our analysis of data on the ipsilateral and contralateral breast recurrence, though being conclusive only under the model assumptions, suggests that the dependence of risks is negligible for the two typcs of local failure.AMS 1980 subject classification