Primary Contralateral Breast Cancer Research Articles

Monitoring for Breast Cancer Recurrence Following Goldilocks Breast Reconstruction

Background The Goldilocks breast reconstruction utilizes redundant mastectomy skin flaps to fashion a breast mound; however, there is concern that imbrication of these skin flaps may predispose to fat necrosis and make detection of local breast cancer recurrence more difficult. Goldilocks patients follow a traditional postmastectomy screening pathway that includes clinical examination for locoregional recurrence, but it is unclear if this is sufficient. We evaluate our Goldilocks reconstruction case series to determine rates of diagnostic imaging, biopsy, and locoregional and distant recurrence. Methods Sixty-six patients (94 breasts) undergoing Goldilocks breast reconstruction were retrospectively reviewed. Any diagnostic postoperative imaging/biopsies performed and that confirmed local or distant breast cancer recurrence were noted. Results Average time of follow-up was 45 months. Most patients in this cohort had stage 0 (27.3%) or stage I (40.9%) breast cancer. There were a total of 11 (11.7%) concerning breast masses identified. Seven (7.4%) masses were biopsied, of which 5 were benign and 2 were invasive cancer recurrence. Four masses (4.3%) underwent diagnostic imaging only, all with benign findings. Five patients in this series were found to have either distant disease or a second primary cancer in the nonoperative contralateral breast. Conclusions Rates of local recurrence following Goldilocks are not higher than expected after other types of postmastectomy reconstruction. Clinical monitoring successfully detected local recurrence in all affected patients in this series. More definite guidelines around the routine screening of Goldilocks mastectomy patients may aid in early detection of local breast cancer recurrence.

Breast cancer polygenic risk score and patient survival outcomes in the Pathways study.

10502 Background: Many common, low-penetrance variants have been identified for breast cancer risk through genome-wide association studies, leading to the development of polygenic scores (PGS) to aggregate the effects of individual variants for risk prediction. Much less is known about genetic determinants of breast cancer-related outcomes. We hypothesized that breast cancer patients with high breast cancer PGS are at risk of a second breast-related adverse event, such as recurrence, contralateral breast cancer, or death. Methods: The Pathways Study is a prospective cohort study of breast cancer survivors enrolled shortly after diagnosis in 2006-2013 at Kaiser Permanente Northern California, with ongoing follow-up. Genome-wide genotype data were available from 3,995 patients for calculation of 4 PGS, including PGS313, PGS4k, PGS5k, and PGS6m. Scores were categorized into tertiles to investigate their associations with 7 survival outcomes including recurrence, contralateral second primary breast cancer, other second primary cancer, and death. Hazard ratios (HR) and 95% confidence intervals (CI) were derived from multivariable Cox proportional hazards regression models. Results: The median age at diagnosis was 60 (23.6-94.8) years, and most (68%) self-identified as White. Many women had estrogen receptor (ER)+ (83.4%), stage I and II tumors (89%), with 13.3% HER2+ tumors. The majority (60%) received lumpectomy and some type of adjuvant therapy (44.3% radiotherapy, 47.0% chemotherapy, and 74.6% received hormonal therapy). By December 31, 2021, the median follow-up time was 10.5 (0.2-14.2) years, with 504 recurrences, 419 total second primary cancers, 146 contralateral second primary breast cancers, 237 non-breast second primary cancers, and 762 deaths (352 breast cancer-specific deaths) observed. In Table 1, patients with medium (T2) and high (T3) PGS313 had higher risk of recurrence, but not contralateral breast cancer or other second primary cancer. They also had higher risk of all-cause death, breast cancer-specific death, total breast cancer event, and invasive disease. The other 3 PGS were not associated with survival outcomes examined. Conclusions: Our study reveals that breast cancer patients with higher PGS313 had higher risk of recurrence, total breast cancer and invasive breast cancer events, and death. These findings highlight a potential role of breast cancer PGS for prognosis, warranting further exploration. [Table: see text]

Short-Term Biomarker Modulation Study of Dasatinib for Estrogen Receptor-Negative Breast Cancer Chemoprevention.

Risk-reducing therapy with selective estrogen receptor (ER) modulators and aromatase inhibitors reduce breast cancer risk. However, the effects are limited to ER-positive breast cancer. Therefore, new agents with improved toxicity profiles that reduce the risk in ER-negative breast cancers are urgently needed. The aim of this prospective, short-term, prevention study was to evaluate the effect of dasatinib, an inhibitor of the tyrosine kinase Src, on biomarkers in normal (but increased risk) breast tissue and serum of women at high risk for a second, contralateral primary breast cancer. Women with a history of unilateral stage I, II, or III ER-negative breast cancer, having no active disease, and who completed all adjuvant therapies were eligible. Patients underwent baseline fine-needle aspiration (FNA) of the contralateral breast and serum collection for biomarker analysis and were randomized to receive either no treatment (control) or dasatinib at 40 or 80 mg/day for three months. After three months, serum collection and breast FNA were repeated. Planned biomarker analysis consisted of changes in cytology and Ki-67 on breast FNA, and changes in serum levels of insulin-like growth factor 1 (IGF-1), IGF-binding protein 1, and IGF-binding protein 3. The primary objective was to evaluate changes in Ki-67 and secondary objective included changes in cytology in breast tissue and IGF-related serum biomarkers. Toxicity was also evaluated. Twenty-three patients started their assigned treatments. Compliance during the study was high, with 86.9% (20/23) of patients completing their assigned doses. Dasatinib was well tolerated and no drug-related grade 3 and 4 adverse events were observed. Since only one patient met the adequacy criteria for the paired FNA sample, we could not evaluate Ki-67 level or cytological changes. No significant change in serum biomarkers was observed among the three groups. Dasatinib was well tolerated but did not induce any significant changes in serum biomarkers. The study could not fulfill its primary objective due to an inadequate number of paired FNA samples. Further, larger studies are needed to evaluate the effectiveness of Src inhibitors in breast cancer prevention.

Mode of Detection of Second Events in Routine Surveillance of Early Stage Breast Cancer Patients

IntroductionNCCN and ASCO guidelines recommend breast cancer (BC) follow-up to include clinical breast examination (CBE) every 6 months and annual mammography (AM) for 5 years. Given limited data to support CBE, we evaluated the modes of detection (MOD) of BC-events in a contemporary practice. MethodsWe conducted a retrospective review of registry patients with early stage BC (DCIS, Stage I or II) diagnosed between 2010 and 2015 with at least 5 years of follow-up. Second events were defined as malignant (contralateral primary, ipsilateral breast tumor recurrence (IBTR), chest wall recurrence, regional node recurrence or distant relapse) or benign. MOD was categorized as patient complaint, clinical examination or breast imaging. ResultsSixty-three of 351 BC patients experienced second events. 15 had BC malignant events, including 4 distant disease, 5 contralateral primary, and 3 IBTR. 7/8 of IBTR and contralateral primary BC were AM detected. Patient complaints identified 4/4 distant relapses. Clinical exam identified 2/2 chest wall recurrences in post-mastectomy patients. ConclusionsOnly 2.8% (10/351) of early stage BC patients experienced recurrence during 5 years of follow-up. AM was the predominate MOD of both IBTR and new contralateral primary following breast conserving therapy. Patient complaints prompted evaluation for distant disease. Provider CBE was MOD in only 2/351, 0.6% 95% CI (2.1%-0.1%) of patients as chest wall recurrences postmastectomy. Given modern enhancements to imaging and lower recurrence rates, this data encourages the reassessment of guidelines for every 6-month CBE and provides basis to study telehealth in survivorship care.

Mammographic texture features associated with contralateral breast cancer in the WECARE Study

To evaluate whether mammographic texture features were associated with second primary contralateral breast cancer (CBC) risk, we created a “texture risk score” using pre-treatment mammograms in a case–control study of 212 women with CBC and 223 controls with unilateral breast cancer. The texture risk score was associated with CBC (odds per adjusted standard deviation = 1.25, 95% CI 1.01–1.56) after adjustment for mammographic percent density and confounders. These results support the potential of texture features for CBC risk assessment of breast cancer survivors.

Smoking, Radiation Therapy, and Contralateral Breast Cancer Risk in Young Women.

Evidence is mounting that cigarette smoking contributes to second primary contralateral breast cancer (CBC) risk. Whether radiation therapy (RT) interacts with smoking to modify this risk is unknown. In this multicenter, individually matched, case-control study, we examined the association between RT, smoking, and CBC risk. The study included 1521 CBC cases and 2212 controls with unilateral breast cancer, all diagnosed with first invasive breast cancer between 1985 and 2008 aged younger than 55 years. Absorbed radiation doses to contralateral breast regions were estimated with thermoluminescent dosimeters in tissue-equivalent anthropomorphic phantoms, and smoking history was collected by interview. Rate ratios (RRs) and 95% confidence intervals (CIs) for CBC risk were estimated by multivariable conditional logistic regression. There was no interaction between any measure of smoking with RT to increase CBC risk (eg, the interaction of continuous RT dose with smoking at first breast cancer diagnosis [ever/never]: RR = 1.00, 95% CI = 0.89 to 1.14; continuous RT dose with years smoked: RR = 1.00, 95% CI = 0.99 to 1.01; and continuous RT dose with lifetime pack-years: RR = 1.00, 95% CI = 0.99 to 1.01). There was no evidence that RT further increased CBC risk in young women with first primary breast cancer who were current smokers or had smoking history.

Race, ethnicity and risk of second primary contralateral breast cancer in the United States.

Breast cancer survivors have a high risk of a second primary contralateral breast cancer (CBC), but there are few studies of CBC risk in racial/ethnic minority populations. We examined whether the incidence and risk factors for CBC differed by race/ethnicity in the United States. Women with a first invasive Stage I-IIB breast cancer diagnosis at ages 20-74 years between 2000 and 2015 in the Surveillance, Epidemiology, and End Results Program (SEER) 18 registries were followed through 2016 for a diagnosis of invasive CBC ≥1 year after the first breast cancer diagnosis. We used cause-specific Cox proportional hazards models to test the association between race/ethnicity and CBC, adjusting for age, hormone receptor status, radiation therapy, chemotherapy and stage at first diagnosis, and evaluated the impact of contralateral prophylactic mastectomy, socioeconomic status, and insurance status on the association. After a median follow-up of 5.9 years, 9247 women (2.0%) were diagnosed with CBC. Relative to non-Hispanic (NH) White women, CBC risk was increased in NH Black women (hazard ratio = 1.44, 95% CI 1.35-1.54) and Hispanic women (1.11, 95% CI 1.02-1.20), with the largest differences among women diagnosed at younger ages. Adjustment for contralateral prophylactic mastectomy, socioeconomic status and health insurance did not explain the associations. Therefore, non-Hispanic Black and Hispanic women have an increased risk of CBC that is not explained by clinical or socioeconomic factors collected in SEER. Large studies of diverse breast cancer survivors with detailed data on treatment delivery and adherence are needed to inform interventions to reduce this disparity.

36P Survival in patients with contralateral breast cancer

Survival in patients with contralateral breast cancer Kamishov S.V., Izrailbekova K.Sh. Republican Specialized Scientific and Practical Medical Center of Oncology and Radiology of the Ministry of Health of the Republic of Uzbekistan, Tashkent. Survival data are not readily available in many developing countries due to inadequate information systems to collect reliable data on cancer mortality. Not all cancer patients die from cancer. Thus, cancer and other causes of death act independently or simultaneously. A cohort study was conducted to identify risk factors for contralateral breast cancer and to determine whether there was any significant difference in survival among patients with unilateral breast cancer (UBC) and patients with primary contralateral breast cancer (PCBC). The study group consisted of patients with breast carcinoma as the first invasive primary cancer, diagnosed in 2012-2019 (n = 3492) at the Republican Special Medical Center for Medical and Rehabilitation of Uzbekistan, Tashkent). They were under surveillance until December 31, 2019. All patients undergoing treatment are monitored in accordance with the observation protocols of the Republican Specialized Scientific and Practical Medical Center of Oncology and Radiology of the Ministry of Health of the Republic of Uzbekistan In this study, the follow-up loss was 10% in UBC patients and 7.5% in PCBC patients. A total of 3492 cases of breast cancer were diagnosed at the RSPMCHR from 2012-2019. The analysis included all patients with UBC who did not develop a second cancer (n = 3163) and patients with PCBC who developed contralateral breast cancer (n = 67). The relative survival rates between younger, middle-aged, and older women with PCBC were significantly different from each other (p = 0.001). The differences in the relative survival rates of young, middle-aged and older women with UBC were not statistically significant (p = 0.4). Despite the small sample size, the present study shows that early diagnosis has a survival advantage in breast cancer. In addition to organizing mammographic screening, in developing countries, educational programs are needed to raise awareness of cancer in order to detect breast cancer at an early stage and reduce mortality.

Breast cancer with an intraductal component that was proven genetically to be metastasis of contralateral breast cancer: a case report

BackgroundWhen diagnosing patients with bilateral breast cancer, it is challenging to determine the relationship between multiple breast cancer lesions at the individual patient level with certainty.Case presentationA 35-year-old Japanese woman was diagnosed with a left breast cancer. She was previously diagnosed with right pT3N3M0 stage IIIC breast cancer and underwent chemotherapy with targeted therapy, radiotherapy, and endocrine therapy as adjuvant treatment after mastectomy and axillary lymph node dissection. Approximately 2 years after the first surgery, her left breast cancer was preoperatively diagnosed as a contralateral primary breast cancer, and left mastectomy and axillary lymph node dissection were performed. Histopathologically, the tumor was determined to be invasive ductal carcinoma accompanied with several intraductal components. After a second surgery, mutation analysis of her bilateral breast cancer was performed in a clinical study, which revealed that her metachronous bilateral breast tumors had the same GATA3 and CSMD1 mutations. Thus, mutation analysis strongly supported her latter left breast cancer being a metastatic lesion from the former right breast cancer. Some difficulties in diagnosing bilateral breast cancer exist when determining whether they are double primary cancers or represent contralateral breast metastasis. The existence of intraductal components is a critical piece of information for suspecting primary lesions. However, this case demonstrated that metastatic contralateral breast lesions can have intraductal components.ConclusionHerein we report a genetically proven contralateral breast metastasis with some intraductal components.

Abstract P5-12-05: Clinical outcomes in early breast cancer patients on adjuvant tamoxifen: Impact of CYP2D6 genotype and observed endoxifen concentrations

Abstract Background: Tamoxifen is widely used in patients with hormone sensitive breast cancer in the adjuvant setting to decrease risk of recurrence and metastasis. 5-10 years of tamoxifen has demonstrated a near 50% reduction in recurrence risk. Despite marked interpatient variation in the metabolism of tamoxifen to its active metabolite endoxifen, all patients are prescribed 20 mg daily dose of tamoxifen. Current evidence suggests that patients are at risk for suboptimal benefit if measured endoxifen concentration is below 5.9 ng/ml (~15nM). However, there have been conflicting data on the clinical utility of CYP2D6 genotype testing, and measuring endoxifen plasma concentration as a predictor of breast cancer recurrence. The goal of this prospective study was to determine the impact of endoxifen levels and CYP2D6 genetic variations to clinical outcome among patients with early breast cancer. Methods: Since 2010, as part of Personalized Medicine Program in Oncology, our team has been prospectively enrolling patients on tamoxifen therapy. To date 950 patients have been enrolled and preliminary analysis has been completed in 429. After initial CYP2D6 genotype testing, plasma concentration of tamoxifen and its metabolites were quantified using liquid chromatography-tandem mass spectrometry during each clinic visit. Baseline characteristic are outlined in table 1. Primary outcome assessed was invasive disease-free survival (IDFS) defined as time since start of tamoxifen therapy till an event of interest such as loco-regional recurrence, distant metastasis, new contralateral primary breast cancer, death due to breast cancer and other causes. Patients were censored at their last encounter at our institution (London Health Sciences Centre). Results: IDFS data for 426 patients were obtained. Outcome was stratified by CYP2D6 phenotypes (ultra-rapid, extensive, intermediate and poor metabolizers) and endoxifen levels (>5.9ng/ml or <5.9ng/ml). CYP2D6 phenotype did not demonstrate a significant association for IDFS. However, Kaplan Meier analysis stratified for endoxifen concentration >vs< 5.9 ng/ml showed a clear trend towards lower IDFS (hazard ratio = 2.4, (95%CI,1.26-4.77) P=0.0002) among those with endoxifen < 5.9 ng/ml. We note this preliminary data analysis was unadjusted and will undergo further in-depth statistical analysis. Conclusion: Preliminary finding suggests endoxifen concentration, but not CYP2D6 phenotype, may be a predictor of risk for suboptimal benefit during tamoxifen therapy. Detailed statistical analysis is planned for the full cohort, including adjustment for covariates including tumor stage, menopausal status, drug interactions, and use of aromatase inhibitors. To our knowledge, this is the first study of its type to prospectively collect multiple plasma samples for tamoxifen and endoxifen level in real-world patients during tamoxifen therapy, with sufficient sample size and follow-up period for primary clinical outcome. Table 1: Baseline Characteristics of PatientsCharacteristicsCYP2D6-Phenotypes, n=429 (%)Endoxifen concentration, n=429 (%)UM/EMIMPM>5.9ng/ml(~15nm)<5.9ng/ml(~15nm)n= 256n= 153n= 20n=376n= 53Age at DiagnosisMean5049485048Range24-8928-7928-8324-8427-88SexMale3 (1)7(5)08(2)2(4)Female253 (99)146(95)20(100)368(98)51(96)Tumor statusT1121(47)70(46)9(45)177(47)23(43)T297(38)58(38)10(50)142(38)23(43)T318(7)16(10)1(5)30(8)5(9)T412(5)4(3)016(4)0unknown8(3)5(3)011(3)2(4)Nodal statusN0124(97)71(46)10(50)179(48)26(49)N195 (37)53(35)9(45)144(38)13(24)N217(7)18(12)1(5)28(7)8(15)N313(5)5(3)015(4)3(6)Unknown7(3)6(4)010(3)3(6)HistologyIDC205(80)128(84)16(80)303(81)48(91)ILC28(11)14(9)3(15)41(11)3(6)other5(2)2(1)06(2)0unknown18(7)9(6)1(5)26(7)2(4)Grade154(21)24(16)3(15)78(21)3(6)2139(54)84(55)13(65)202(54)34(64)354(21)39(25)4(20)84(3)13(24)unknown9(4)6(4)012(3)3(6)ER+251(98)151(99)20(100)369(98)53(100)-5(2)2(1)07(2)0unknown00000PR+232(90)142(93)20(100)343(91)51(96)-24(9)11(7)033(9)2(4)unknown00000Her2+55(21)25(16)5(25)75(20)10(19)-200(78)127(84)15(75)299(80)43(81)unknown1102(1)0Breast SurgeryMastectomy149(58)84(55)11(55)214(57)30(57)Lumpectomy105(41)68(44)9(45)159(42)23(43)Unknown2(1)103(1)0Axillary SurgerySLNB137(54)80(52)12(60)204(54)25(47)ALND113(44)70(46)8(40)165(44)26(49)Unknown6(2)3(2)07(2)2(4)Chemotherapy190(74)108(71)16(80)277(74)37(70)Radiation Therapy213(83)126(82)17(85)310(82)46(87)Herceptin57(22)23(15)6(30)77(16)9(17) Citation Format: Veera Durga Sravanthi Panuganty, Denise Keller, Wendy A Teft, John Gordon Lenehan, Kylea Raijann Potvin, Jawaid Younus, Theodorus Anthony Vandenberg, Diane Mary Logan, Karin Hahn, Muriel Brackstone, Phillip Stanley Blanchette, Francisco Perera, Yun-Hee Choi, Richard Brian Kim. Clinical outcomes in early breast cancer patients on adjuvant tamoxifen: Impact of CYP2D6 genotype and observed endoxifen concentrations [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 P5-12-05.

Bilateral breast cancer: a case study

AbstractBackground:Breast cancer is the most common cancer among females worldwide. Increasing breast cancer incidence rates, improved diagnosis and management modalities and growing life expectancy have resulted in increasing numbers of women at risk of developing contralateral primary breast cancer. Bilateral breast cancer can occur synchronously or metachronously.Material and methods:This study reports three cases of bilateral breast cancer patients treated at our oncology department between March 2018 and March 2019. The features of presentation, investigation, diagnosis and follow-up care are the highlights of this study.Results:Bilateral breast cancer was noted in three patients among the study population in the age group of 35 –55 years. Two of these patients had metachronous bilateral breast cancer, and one patient developed cancer in the second breast during the course of management. The second breast cancers differed histologically from primary breast cancer.Conclusion:Poor awareness on breast cancer care and the lack of national screening guidelines and programmes, and poor infrastructure, all contribute to late presentation and difficult breast cancer management. Proper history, clinical examination and imaging of opposite breast should be done to ensure adequate and timely management of bilateral breast cancer.

Association of a Pathway-Specific Genetic Risk Score With Risk of Radiation-Associated Contralateral Breast Cancer

Radiation therapy for breast cancer is associated with increased risk of a second primary contralateral breast cancer, but the genetic factors modifying this association are not well understood. To determine whether a genetic risk score comprising single nucleotide polymorphisms in the nonhomologous end-joining DNA repair pathway is associated with radiation-associated contralateral breast cancer. This case-control study included a case group of women with contralateral breast cancer that was diagnosed at least 1 year after a first primary breast cancer who were individually matched to a control group of women with unilateral breast cancer. Inclusion criteria were receiving a first invasive breast cancer diagnosis prior to age 55 years between 1985 and 2008. Women were recruited through 8 population-based cancer registries in the United States, Canada, and Denmark as part of the Women's Environment, Cancer, and Radiation Epidemiology Studies I (November 2000 to August 2004) and II (March 2010 to December 2012). Data analysis was conducted from July 2017 to August 2019. Stray radiation dose to the contralateral breast during radiation therapy for the first breast cancer. A novel genetic risk score comprised of genetic variants in the nonhomologous end-joining DNA repair pathway was considered the potential effect modifier, dichotomized as high risk if the score was above the median of 74 and low risk if the score was at or below the median. The main outcome was risk of contralateral breast cancer associated with stray radiation dose stratified by genetic risk score, age, and latency. A total of 5953 women were approached for study participation, and 3732 women (62.7%) agreed to participate. The median (range) age at first diagnosis was 46 (23-54) years. After 5 years of latency or more, among women who received the first diagnosis when they were younger than 40 years, exposure to 1.0 Gy (to convert to rad, multiply by 100) or more of stray radiation was associated with a 2-fold increased risk of contralateral breast cancer compared with women who were not exposed (rate ratio, 2.0 [95% CI, 1.1-3.6]). The risk was higher among women with a genetic risk score above the median (rate ratio, 3.0 [95% CI, 1.1-8.1]), and there was no association among women with a genetic risk score below the median (rate ratio, 1.3 [95% CI, 0.5-3.7]). Among younger women with a high genetic risk score, the attributable increased risk for contralateral breast cancer associated with stray radiation dose was 28%. This study found an increased risk of contralateral breast cancer that was attributable to stray radiation exposure among women with a high genetic risk score and who received a first breast cancer diagnosis when they were younger than 40 years after 5 years or more of latency. This genetic risk score may help guide treatment and surveillance for women with breast cancer.

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.

Second malignancy in young early-stage breast cancer patients with modern radiotherapy: A long-term population-based study (A STROBE-compliant study).

Second cancer is a leading cause of death in long-term survivors of younger early-stage breast cancer patients. To date, relationship of age, receipt of radiotherapy (RT), and estimated doses received by target organs have not yet been well elucidated. Using Surveillance, Epidemiology, and End Results database, patients aged 20 to 44, diagnosed with a first primary staging I-IIIA ipsilateral breast invasive ductal carcinoma, underwent surgery during 1988 to 2009 were identified, and those with a second malignancy at ≥1-year follow-up were analyzed to calculate cumulative incidences (CIs) of second malignancy in whole group and each subgroup. Subgroups were dichotomized by surgery type, axillary dissection, and axillary lymph node status. With a median follow-up of 11.8 years, 22,628 women including 1495 patients (6.6%) developing second malignancies (3.7% contralateral breast cancer, 2.9% non-breast second malignancies, and 0.7% high-dose site second malignancies) were identified. Three-dimensional coordinate systems with age at primary diagnosis, time after primary breast cancer diagnosis, and CI of second malignancy as 3 axes, for endpoints including all second malignancy, second primary contralateral breast cancer, and non-breast second malignancy were presented, along with the risk in RT and non-RT groups in overall group and subgroups. Five-, 10-, 15-, and 20-year all second malignancy-free survivals in RT and non-RT groups were 89.5% versus 85.4%, 80.1% versus 75.0%, 72.9% versus 67.9%, and 65.6% versus 61.8% (P < .0001). From the large national dataset, a broad visualized overview of second malignancy risk, including second contralateral breast cancer and non-breast second cancer, suggests generally beneficial therapeutic ratio for radiotherapy in young women with early-stage breast cancer.

Use of Antihypertensive Medications and Risk of Adverse Breast Cancer Outcomes in a SEER-Medicare Population.

Background: It is unclear if use of common antihypertensive medications influences the risk of adverse breast cancer outcomes.Methods: Using the linked Surveillance, Epidemiology and End-Results (SEER)-Medicare database, we identified 14,766 women between ages 66 and 80 years diagnosed with incident stage I/II breast cancer between 2007 and 2011. Medicare Part D data were obtained to characterize women's post-cancer use of various antihypertensive medications. Outcomes included a second breast cancer event (SBCE; a composite outcome defined as the first of a recurrence or a second contralateral primary breast cancer), breast cancer recurrence, and breast cancer-specific mortality. Time-varying Cox proportional hazard models were used to estimate hazard ratios (HR) and their associated 95% confidence intervals (CI).Results: There were 791 SBCEs, 627 breast cancer recurrences, and 237 breast cancer deaths identified over a median follow-up of 3 years. Use of diuretics (n = 8,517) after breast cancer diagnosis was associated with 29% (95% CI, 1.10-1.51), 36% (95% CI, 1.14-1.63) and 51% (95% CI, 1.11-2.04) higher risks of a SBCE, recurrence, and breast cancer death, respectively. Compared with nonusers, β-blockers users (n = 7,145) had a 41% (95% CI, 1.07-1.84) higher risk of breast cancer death. Use of angiotensin II receptor blockers, calcium channel blockers and angiotensin-converting enzyme inhibitors were not associated with risks of breast cancer outcomes.Conclusions: Use of diuretics and β-blockers may be associated with increased risk of breast cancer outcomes among older women.Impact: Most antihypertensive medications are safe with respect to breast cancer outcomes, but more research is needed for diuretics and β-blockers. Cancer Epidemiol Biomarkers Prev; 26(11); 1603-10. ©2017 AACR.

The psychosocial impact of contralateral risk reducing mastectomy (CRRM) on women: A rapid review

For women who have been diagnosed with unilateral breast cancer, there is an increasing trend for them to request removal of the contralateral healthy breast, the so-called contralateral risk reducing mastectomy (CRRM). The current literature is only just beginning to identify patient-reported reasons for undergoing CRRM and associated patient-reported outcomes. It is also unclear whether women at moderate/high risk of developing a subsequent primary contralateral breast cancer report similar outcomes to those considered to be at low/average risk. This lack of knowledge provides the rationale for this review. A rapid review methodology was undertaken to identify and explore the published research literature focused on the longer term (>5y) psychosocial impacts on women who undergo CRRM. Fifteen studies were identified. No UK studies were identified. High satisfaction and psychosocial well-being were consistently reported across all studies. Reducing the risk of a subsequent contralateral breast cancer and therefore reducing cancer-related anxiety, and satisfaction with cosmesis, were key themes running across all studies explaining satisfaction. Dissatisfaction was associated with adverse effects such as poor cosmesis, body image changes, femininity, sexual relationships, reoperations for acute and longer term complications, and reconstructive problems. Satisfaction and psychological well-being following CRRM was consistently high across all studies. However, the findings suggest women need to be more fully informed of the risks and benefits of CRRM and/or immediate/delayed reconstruction to support informed decision making.

Issues in Breast Cancer Survivorship: Optimal Care, Bone Health, and Lifestyle Modifications.

There are an estimated 3.1 million survivors of breast cancer in the United States. The predominant reasons for this substantially large population are that breast cancer is the most common noncutaneous malignancy among women and that 5-year survival rates after breast cancer treatment are approximately 90%. These patients have many medical considerations, including the need to monitor for disease recurrence and to manage complications of their previous cancer treatments. Most patients remain at risk indefinitely for local and systemic recurrences of their breast cancers and have an increased risk of developing contralateral new primary breast cancers. Therefore, optimizing care for this patient population is critical to the overall health care landscape in the United States. Here, we summarize survivorship care delivery and its challenges, the optimization of bone health in breast cancer survivors, and opportunities for risk reduction through lifestyle modifications.

PPAC (programme personnalisé de l’après-cancer) : rationnel et mise en place

The growing number of breast cancer survivors challenges healthcare organizations, particularly oncology specialty and primary care providers. Currently, in France, the follow-up care is based on detection of recurrences, of second primary contralateral breast cancer, of long-term treatment sequelae, in addition to psychosocial consequences of cancer and its treatment. This review will discuss the evidence base and intents of breast cancer survivorship care plans (CSCPs) as a wellness model for cancer survivors in clinical setting, mainly providing health promotion recommendations such as regular exercise. The CPCPs involve multidisciplinary approach and patient–physician communication. Therefore, this comprehensive care will improve their quality of life, treatment compliance, and general health care maintenance. This article offers innovative guidance to implement the post-cancer patient care and includes the relevant templates to be submitted to the patients.

Abstract P5-12-01: Adjuvant endocrine therapy and risk of contralateral breast cancer among a cohort of U.S. women with breast cancer

Abstract Background: The increasing incidence of estrogen receptor (ER)-positive breast cancer in the U.S. in concert with the aging population and improved survival have resulted in an increased number of women at risk of developing a second contralateral primary breast cancer. Results from randomized clinical trials have suggested a reduced risk of contralateral breast cancer among women taking tamoxifen or aromatase inhibitors. However, little is known about the duration of beneficial effects of endocrine therapy within the context of real life treatment scenarios, where gaps in treatment and varying durations of use may influence risk. Methods: We assessed contralateral breast cancer risk associated with adjuvant tamoxifen treatment among a cohort of 7,541 women, ages 24-85 years, who were members of Kaiser Permanente (KP) Northwest or Colorado, and were diagnosed with invasive breast cancer between 1990 and 2008 and remained at risk of contralateral breast cancer for at least one year. We also assessed risk in relation to aromatase inhibitor use, though statistical power was somewhat limited due to the relatively recent introduction of aromatase inhibitors in this older cohort. Use of tamoxifen, aromatase inhibitors and other treatments was ascertained from KP prescription and medical records. Relative risks (RR) and 95% confidence intervals (CI) were estimated using multivariable Poisson regression adjusting for study site, age at and year of diagnosis, stage at diagnosis, ER status, chemotherapy, and radiotherapy. Results: Over a median (range) of 6.3 (1.0-20.9) years of follow-up, 248 women developed contralateral breast cancer. Among patients surviving at least five years (n=4,668), 58% were prescribed tamoxifen with a median (range) duration of use of 4.2 (0.25-16.2) years. In models evaluating joint effects of tamoxifen duration and time since last use, we observed a statistically significant reduced risk of contralateral breast cancer among current tamoxifen users (RR=0.47, 95% CI: 0.30, 0.74) and among former users with 4+ years of tamoxifen (RR=0.39, 95% CI: 0.24, 0.63) as compared with women not treated with tamoxifen. Former users with 1-4 years of tamoxifen demonstrated a suggestive reduction in risk (RR=0.71, 95% CI: 0.45, 1.10), but there was no evidence of risk reduction for former users with &amp;lt;1 year of tamoxifen (RR=0.96, 95% CI: 0.56, 1.64). The reduced risks associated with 4+ years of tamoxifen persisted among patients surviving at least 7 years but were attenuated among those with more than 10 years since their first primary diagnosis. Aromatase inhibitor use was also associated with reduced contralateral breast cancer risk (RR=0.46, 95% CI: 0.22, 0.97). In subgroup analyses restricted to women whose first primary cancer was ER-positive (n=5,951), findings were consistent with those observed in the overall cohort. Conclusions: Adjuvant tamoxifen and aromatase inhibitor therapy considerably reduce the risk of contralateral breast cancer. Furthermore, our data suggest that tamoxifen protects against contralateral breast cancer while women are being treated and that the protective effect appears to continue after cessation with longer durations of use. Citation Format: Gierach GL, Curtis RE, Pfeiffer RM, Mullooly M, Hoover RN, Nyante SJ, Feigelson HS, Glass AG, Berrington de Gonzalez A. Adjuvant endocrine therapy and risk of contralateral breast cancer among a cohort of U.S. women with breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-12-01.

Issues in Breast Cancer Survivorship: Optimal Care, Bone Health, and Lifestyle Modifications

There are an estimated 3.1 million survivors of breast cancer in the United States. The predominant reasons for this substantially large population are that breast cancer is the most common noncutaneous malignancy among women and that 5-year survival rates after breast cancer treatment are approximately 90%. These patients have many medical considerations, including the need to monitor for disease recurrence and to manage complications of their previous cancer treatments. Most patients remain at risk indefinitely for local and systemic recurrences of their breast cancers and have an increased risk of developing contralateral new primary breast cancers. Therefore, optimizing care for this patient population is critical to the overall health care landscape in the United States. Here, we summarize survivorship care delivery and its challenges, the optimization of bone health in breast cancer survivors, and opportunities for risk reduction through lifestyle modifications.