Synchronous and metachronous bilateral breast cancer among women with a history of lobular carcinoma in situ.

PURPOSE: Lobular carcinoma in situ (LCIS) confers increased cancer risk in either breast, but it remains unclear if this population is at increased risk for bilateral breast cancer (BC) development. Here we report bilateral BC incidence among women with a history of LCIS. METHODS: Women with classic-type LCIS diagnosed from 1980 to 2017 who developed unilateral BC (UBC) or bilateral BC were identified. Bilateral BC was categorized as synchronous (bilateral BC diagnosed < 6 months apart; SBBC) or metachronous (bilateral BC diagnosed ≥ 6 months apart; MBBC). Five-year incidence rates of bilateral BC among this population were evaluated. Comparisons were made to identify factors associated with bilateral BC. RESULTS: At 7 years' median follow-up, 249/1651 (15%) women with LCIS developed BC; 34 with bilateral BC (2%). There were no clinicopathologic feature differences between those with UBC and bilateral BC. SBBC occurred in 18 without significant differences versus UBC. Among 211 with UBC and a contralateral breast at risk, 16 developed MBBC at a median follow-up of 3 years. MBBC patients were less likely to receive endocrine therapy and more likely to receive chemotherapy versus UBC. Tumor histology was not associated with MBBC. Estimated 5-year MBBC risk was 6.4%. Index estrogen/progesterone receptor positivity and endocrine therapy were the only factors associated with MBBC risk. CONCLUSION: Bilateral BC occurred in 2% of women with LCIS history at median follow-up of 7 years. Similar to the general BC population, a decrease in MBBC is seen among women with a history of LCIS who develop hormone receptor-positive disease and those who receive endocrine therapy, highlighting the protective effects of this treatment.

Risk management recommendations and patient acceptance vary with high-risk breast lesions.

INTRODUCTION: Lobular carcinoma in situ (LCIS), atypical ductal and lobular hyperplasia (AH) increase breast cancer risk. We examined risk management recommendations (RMR) and acceptance in AH/LCIS. METHODS: All patients with AH/LCIS on core needle biopsy from 2013 to 2016 at our institution were identified; cancer patients were excluded. Univariate and multivariate analysis examined factors associated with management. RESULTS: 98 % of patients were evaluated by breast surgeons and 53 % underwent risk model calculation (RC). 77 % had new RMR. RMR of MRI screening (MRI), genetic counselling (GC) and medical oncology (MO) referral were 41 %, 18 %, 77 %, respectively. MRI screening was more likely recommended in those with strong family history (p = 0.01), and high RC (p < 0.001). Uptake of at least one RMR did not occur in 84 % of patients. Use of RC correlated with MO acceptance (p = 0.049). CONCLUSIONS: Diagnosis of atypia has the potential to change risk management for most, however only 16 % of patients accepted all RMR.

Trends in incidence, treatment, survival and subsequent breast cancer in lobular carcinoma in situ in the Netherlands: A population-based analysis.

PURPOSE: We analysed incidence, treatment, survival, occurrence of ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC) after lobular carcinoma in situ (LCIS) in the Netherlands. METHODS: All women diagnosed with classic LCIS between 1989 and 2017 were identified from the Netherlands Cancer Registry. We calculated overall (OS), relative survival (RS) and cumulative incidence functions (CIF, accounting for competing risks) of mortality, DCIS and IBC. For IBC, standardised incidence ratios (SIR) of IBC were calculated. Analyses were stratified for surgical treatment. RESULTS: We included 1890 patients. Median age was 51 years. Median follow-up was 8.5 years. In 1989-2017, LCIS incidence increased from 41 to 124, surgical treatment decreased from 100% to 41.1 % - mostly BCS. 10-year OS and 20-year RS exceeded 90 % in all subgroups. Overall, 48 (2.5 %) and 270 (14.3 %) patients were diagnosed with DCIS and IBC. IBCs were mostly early-stage. After mastectomy, 13 of 14 IBCs presented contralaterally. In the other groups, 64.8-70.9 % of IBCs presented ipsilaterally, 34.5-53.9 % of these were lobular. The SIR of ipsilateral IBC was highest after no surgery (6.9, 95%CI:4.9-9.4), lowest after mastectomy (0.2, 95%CI:0.4-0.8). CONCLUSION: LCIS incidence increased, surgical treatment decreased. The low mortality risks support consideration of active surveillance. However, the increased IBC incidence suggests careful monitoring.

Lobular intraepithelial neoplasia: Outcomes and optimal management.

INTRODUCTION: Lobular neoplasia is a term encompassing both atypical lobular hyperplasia and lobular carcinoma in situ. These pathological findings are of uncertain malignant potential and predispose to a higher lifetime risk of breast cancer. Debate surrounds the management of such lesions, with the rationale for diagnostic excision based on the possibility of upgrading to malignancy. In this study, we report the upgrade rate of these lesions and risk of subsequent development of breast cancer. METHODS: This is a retrospective review of a prospectively maintained data base of all biopsies of breast screening-detected abnormalities in a single Irish breast-screening unit. We included all patients with lobular neoplasia on core needle biopsy who underwent diagnostic excision from 2005 to 2012. We excluded those who had concurrent high-risk lesions on biopsy. End points included upgrade rate and subsequent diagnosis of malignancy on follow-up. RESULTS: During the study period, 66 patients met criteria for inclusion, with a mean age of 53.74 years. Upgrade rate following excision was 13.64% (n = 9/66). Of those not upgraded, 7.02% (n = 4/57) were subsequently diagnosed with malignancy. Median time to diagnosis was 59.61 months (range = 10.5-124.4). CONCLUSION: There is a significant rate of upgrade following diagnostic excision of lobular neoplasia, supporting the practice of diagnostic excision. There is an increased lifetime risk of breast cancer for women with a diagnosis of lobular neoplasia, with many of these cancers occurring outside the standard five-year monitoring period, suggesting a potential benefit in extending surveillance.

Lesiones papilares intraductales mamarias: nuestra experiencia 2007-2017 / Intraductal papillary lesions of the breast: our experience 2007-2017

OBJETIVOS: Revisión y análisis de los casos de lesiones papilares intraductales mamarias diagnosticados en nuestro centro entre enero del 2007 y diciembre del 2017. Estudiar la asociación de las lesiones papilares con el cáncer de mama. PACIENTES Y MÉTODOS: Estudio descriptivo retrospectivo utilizando la base de datos de Anatomía Patológica. Se incluyó a 135 pacientes que en el periodo descrito tuvieron un diagnóstico anatomopatológico de lesión papilar (papiloma benigno aislado, papilomatosis múltiple, papiloma con carcinoma in situ, papiloma con atipia o carcinoma papilar intraductal). Las variables principales a analizar fueron la edad de las pacientes, las pruebas diagnósticas realizadas, la presencia de lesiones de mayor grado asociadas a la lesión papilar y el desarrollo de neoplasia de mama durante el seguimiento. RESULTADOS: La edad media de las pacientes fue de 50 años. La ductoscopia demostró ser una prueba con alta sensibilidad diagnóstica (88%). En 12 casos (9%) existía carcinoma en la lesión papilar o en sus alrededores (8 carcinomas in situ y 4 infiltrantes) y en 4 casos (3%) encontramos hiperplasia atípica asociada. Con un seguimiento medio de 34 meses, 6 pacientes tuvieron una recidiva en forma de lesión papilar (una papilomatosis múltiple y 5 papilomas), 3 pacientes recidivaron en forma de lesión neoplásica y una paciente desarrolló una neoplasia contralateral. CONCLUSIONES: Ante la sospecha de una lesión papilar y la presencia de secreción por el pezón, debemos considerar la realización de una ductoscopia por su alta sensibilidad. La alta incidencia de una neoplasia asociada a la lesión papilar o su aparición durante el seguimiento justifica su exéresis quirúrgica completa y un seguimiento estricto

OBJECTIVES: To provide a review and analysis of cases of intraductal papillary breast lesions diagnosed at our centre between January 2007 and December 2017, and to study the association between papillary lesions and breast cancer. PATIENTS AND METHODS: We performed a retrospective descriptive study using the pathology database of our centre. We included 135 patients with a pathological diagnosis of papillary lesion (isolated benign papilloma, multiple papillomatosis, papilloma with carcinoma in situ, papilloma with atypia or intraductal papillary carcinoma). The main variables were age, the diagnostic procedures performed, the presence of higher-grade lesions associated with the papillary lesion, and the development of breast neoplasms during follow-up. RESULTS: The patients' mean age was 50 years. Ductoscopy had high sensitivity (88%). Twelve patients (9%) had carcinomas on the papillary lesion or its surrounding areas (8 carcinomas in situ and 4infiltrating carcinomas) and 4 patients (3%) had associated atypical hyperplasia. With a mean follow-up of 34 months, 6 patients had recurrence as a papillary lesion (one multiple papillomatosis and 5papillomas), 3 patients relapsed with a neoplastic lesion, and one patient developed a contralateral neoplasm. CONCLUSIONS: In the presence of a suspected papillary lesion and nipple secretion, ductoscopy should be considered due to its high sensitivity. The high incidence of neoplasms associated with papillary lesions or their development during follow-up justifies their complete surgical excision and strict follow-up

Disparities in Risk Reduction Therapy Recommendations for Young Women With Lobular Carcinoma In-Situ.

BACKGROUND: Endocrine therapy (ET) significantly reduces the risk of breast cancer development in high-risk patients diagnosed with lobular carcinoma in situ (LCIS). However, the variables impacting recommendation and use of ET in young adults (YAs) is not well-studied. We examined the role of provider recommendation and patient acceptance for ET for YAs with LCIS. MATERIALS AND METHODS: The National Cancer Database was queried for women aged < 40 years with primary LCIS between 2000 and 2012. Socioeconomic, demographic, and treatment variables were examined to determine their impact on ET provider recommendation and initial patient acceptance of risk-reducing therapy. RESULTS: Among 1650 YA patients with LCIS, only 749 (45.4%) were recommended ET. On multivariable analysis, women > 30 years of age were more likely recommended ET than women < 30 years (odds ratio [OR], 1.64; 95% confidence interval [CI], 1.10-2.47), African Americans more than other ethnicities (OR, 1.48; 95% CI, 1.1-2.0), and YAs treated in New England were more likely than those in the rest of the country (OR, 3.26; 95% CI, 2.0-5.2). Among YA women recommended ET, only 20.2% had a documented refusal. Only geography appeared to independently impact the likelihood of refusal, with YAs in the Southeastern-Central United States being most likely to refuse ET (OR, 5.4; 95% CI, 1.2-24.0). CONCLUSION: ET is underutilized for risk-reduction in YAs with LCIS. This underuse appears dependent on disparities in provider recommendation practices rather than non-acceptance of therapy. This may reflect regional practice patterns, community standards of care, or provider bias regarding the significance of LCIS as a risk factor for development of invasive cancer.

Psychotropic Medication Use and Postmenopausal Breast Cancer Risk.

BACKGROUND: Prior studies evaluating psychotropic medications in relation to breast cancer risk are inconsistent and have not separately evaluated invasive and in situ disease. METHODS: We estimated hazard ratios (HR) and 95% confidence intervals (CI) for the association of psychotropic medication use (any, typical antipsychotics, atypical antipsychotics, and lithium) with invasive and in situ breast cancer risk among Women's Health Initiative participants (N = 155,737). RESULTS: Prevalence of psychotropic medication use was low (n = 642; 0.4%). During an average 14.8 (SD, 6.5) years of follow-up, 10,067 invasive and 2,285 in situ breast tissues were diagnosed. Any psychotropic medication use was not associated with invasive breast cancer risk compared with nonusers (HR, 0.82; 95% CI, 0.57-1.18). In situ breast cancer risk was higher among "typical" antipsychotic medication users compared with nonusers (HR, 2.05; 95% CI, 0.97-4.30). CONCLUSIONS: These findings do not support an association of psychotropic medication use with invasive breast cancer risk. The possible elevation in in situ breast cancer risk associated with "typical" antipsychotics could not be explained by differences in screening mammography utilization and merits further study. IMPACT: Our findings contribute to knowledge of the safety profile of psychotropic medications and may be useful to clinicians and patients considering use of these medications.

Assessing trends of breast cancer and carcinoma in situ to monitor screening policies in developing settings.

There have been arguments about the role of breast cancer screening at the population level, and some points of controversy have arisen, such the establishment of organized screening policies and the age at which to begin screening. The real benefit of screening has been questioned because the results of this practice may increase the diagnosis of indolent lesions without decreasing mortality due to breast cancer. The authors have proposed a study of incidence and mortality trends for breast cancer in a developing setting in Brazil to monitor the effectiveness of the official recommendations that prioritize the age group from 50 to 69 years. The database of the Cancer Registry and the Mortality Information System was used to calculate age-standardized and age-specific rates, which were then used to calculate incidence and mortality trends using the Joinpoint Regression Program. The results showed stability in trends across all ages and age-specific groups in both incidence and mortality. In conclusion, we found that incidence and mortality rates are compatible with those in regions with similar human development indexes, and trends have demonstrated stabilization. Thus, we do not endorse changes in the official recommendations to conduct screening for ages other than 50 to 69 years, nor should policy makers implement organized screening strategies.

Increasing trends in in situ breast cancer incidence in a region with no population-based mammographic screening program: results from Zurich, Switzerland 2003-2014.

PURPOSE: Increase in in situ breast cancer (BCIS) incidence has been reported across Europe and the USA. However, little is known about the trends in BCIS incidence in regions without population-based mammographic screening programs. We set out to investigate these trends in Zurich, Switzerland, where only opportunistic mammographic screening exists. METHODS: Data from 989 women diagnosed with a primary BCIS between 2003 and 2014 were used in our analyses. Age-standardized incidence rates per 100,000 person-years (ASR) were computed per year. Additional analyses by BCIS subtype, by age group at diagnosis and by incidence period were conducted. Incidence trends over time were assessed using joinpoint regression analysis. RESULTS: The overall BCIS ASR was 10.7 cases per 100,000 person-years with an increasing trend over the study period. A similar trend was observed for the ductal carcinoma in situ (DCIS) ASR, while the lobular carcinoma in situ (LCIS) ASR decreased. Age-specific analyses revealed that the 50-59 year age group had the highest BCIS ASR. The highest increase in BCIS ASR, even though not statistically significant, was observed for the < 40 year age group. CONCLUSIONS: BCIS ASR increased linearly over a 12-year period. The increase was reflected by an increase in DCIS ASR, whereas LCIS ASR decreased over time. The highest increase in BCIS ASR over the study period was observed for the < 40 year age group, even though not statistically significant. Patient and tumor characteristics of this group that may be associated with BCIS development warrant further investigation.

Validation of the IBIS breast cancer risk evaluator for women with lobular carcinoma in-situ.

BACKGROUND: Management advice for women with lobular carcinoma in situ (LCIS) is hampered by the lack of accurate personalised risk estimates for subsequent invasive breast cancer (BC). Prospective validation of the only tool that estimates individual BC risk for a woman with LCIS, the International Breast Cancer Intervention Study Risk Evaluation Tool (IBIS-RET), is lacking. METHODS: Using population-based cancer registry data for 732 women with LCIS, the calibration and discrimination accuracy of IBIS-RET Version 7.2 were assessed. RESULTS: The mean observed 10-year risk of invasive BC was 14.1% (95% CI:11.3%-17.5%). IBIS-RET overestimated invasive BC risk (p = 0.0003) and demonstrated poor discriminatory accuracy (AUC 0.54, 95% CI: 0.48 - 0.62). CONCLUSIONS: Clinicians should understand that IBIS-RET Version 7.2 may overestimate 10-year invasive BC risk for Australian women with LCIS. The newer IBIS-RET Version 8.0, released September 2017, includes mammographic density and may perform better, but validation is needed.

Social relationships, inflammation markers, and breast cancer incidence in the Women's Health Initiative.

OBJECTIVES: Previous research has reported associations between social relationships and carcinogenesis. Inflammation is a potential mediator of these associations. To clarify these links for one tumor site, we examined associations between social relationships, circulating inflammation markers, and breast cancer incidence. MATERIALS AND METHODS: Among 132,262 participants from the prospective Women's Health Initiative, we used linear and logistic regression to evaluate associations between social relationship characteristics (social support, social strain, social network size) and inflammation markers of C-reactive protein (CRP) and white blood cell count (WBC). Cox regression was used to evaluate associations between inflammation markers and breast cancer incidence, as well as associations between social relationship characteristics and breast cancer incidence with and without adjustment for inflammation markers. RESULTS: Larger social networks were associated with lower continuous CRP (beta = -0.22, 95% CI -0.36, -0.08) and WBC (beta = -0.23, 95% CI -0.31, -0.16). Greater social strain was associated with higher continuous CRP (beta = 0.24, 95% CI 0.14, 0.33) and WBC (beta = 0.09, 95% CI 0.04, 0.14). When WBC was dichotomized at 10,000 cells/uL, high WBC was associated with greater hazards of in situ breast cancer (HR = 1.65, 95% CI 1.17, 2.33) but not invasive breast cancer. Social relationship characteristics were not associated with incidence of invasive or in situ breast cancer. CONCLUSION: Larger social networks were associated with lower inflammation and greater social strain was associated with higher inflammation. Higher inflammation might be associated with development of in situ breast cancer, but this appeared to be due to factors other than social relationships.

Breast cancer risk in relation to history of preeclampsia and hyperemesis gravidarum: Prospective analysis in the Generations Study.

Preeclampsia and hyperemesis gravidarum are pregnancy complications associated with altered sex hormone levels. Previous studies suggest preeclampsia may be associated with a decreased risk of subsequent breast cancer and hyperemesis with an increased risk, but the evidence remains unclear. We used data from the Generations Study, a large prospective study of women in the United Kingdom, to estimate relative risks of breast cancer in relation to a history of preeclampsia and hyperemesis using Cox regression adjusting for known breast cancer risk factors. During 7.5 years average follow-up of 82,053 parous women, 1,969 were diagnosed with invasive or in situ breast cancer. Women who had experienced preeclampsia during pregnancy had a significantly decreased risk of premenopausal breast cancer (hazard ratio (HR) =0.67, 95% confidence interval (CI): 0.49-0.90) and of HER2-enriched tumours (HR = 0.33, 95% CI: 0.12-0.91), but there was no association with overall (HR = 0.90, 95% CI: 0.80-1.02) or postmenopausal (HR = 0.97, 95% CI: 0.85-1.12) breast cancer risk. Risk reductions among premenopausal women were strongest within 20 years since the last pregnancy with preeclampsia. Hyperemesis was associated with a significantly increased risk of HER2-enriched tumours (HR = 1.76, 95% CI: 1.07-2.87), but not with other intrinsic subtypes or breast cancer risk overall. These results provide evidence that preeclampsia is associated with a decreased risk of premenopausal and HER2-enriched breast cancer and that hyperemesis, although not associated with breast cancer risk overall, may be associated with raised risk of HER2-enriched tumours.

Family History and Risk of Second Primary Breast Cancer after In Situ Breast Carcinoma.

Background: Incidence rates of in situ breast carcinomas have increased due to widespread adoption of mammography. Very little is known about why some women with in situ breast cancer later develop second primary breast cancers.Methods: In this population-based nested case-control study among in situ breast cancer survivors, including 539 cases with a second primary breast cancer and 994 matched controls, we evaluated the association between first-degree family history of breast cancer and risk of developing a second primary breast cancer.Results: First-degree family history of breast cancer was associated with an increased risk of developing a second primary breast cancer among women with a previous in situ breast cancer [odds ratio (OR) = 1.33, 95% confidence interval (CI), 1.05-1.69] and those with two or more affected first-degree relatives had an even higher risk (OR = 1.94; 95% CI, 1.15-3.28). Those whose relative was diagnosed at less than 50 years old were more likely to develop a second primary breast cancer (OR = 1.78; 95% CI, 1.24-2.57). No difference in risks associated with number or age of affected relatives was observed by menopausal status.Conclusions: Results from this study suggest that first-degree family history of breast cancer may be an important risk factor for development of a second primary breast cancer among women with a previous in situ breast cancer.Impact: Given the growing population of in situ breast cancer survivors, a better understanding of risk factors associated with development of a second primary breast cancer is needed to further understand risk. Cancer Epidemiol Biomarkers Prev; 27(3); 315-20. ©2018 AACR.

Carcinoma In Situ Involving Sclerosing Adenosis: Seeking the Salient Histological Characteristics to Prevent Overdiagnosis.

Ductal or lobular carcinoma in situ (DCIS/LCIS) can rarely arise from sclerosing adenosis (SA). The combination of cytologically malignant cells and the infiltrative growth pattern may make it challenging to distinguish it from an invasive carcinoma. The authors reviewed 50 consecutive cases of CIS involving SA to seek the salient histologic characteristics in order to prevent overdiagnosis. The features commonly seen with CIS were the lobular configuration at low magnification (94%), uninvolved SA in neighboring tissue (84%), at least focally identifiable myoepithelial cells on H&E-stained sections (76%), separate foci of unequivocal CIS (58%), associated microcalcifications (54%), and hyaline basement membrane surrounding tumor cell nests (48%). The group of DCIS with high nuclear grade showed a tendency to occupy the entire lobule of SA, whereas those with non-high grade were more often partially involving the affected lobule. The presence of adjacent separate foci of CIS was more closely related to the DCIS lesions when compared to those of LCIS. The finding of an SA lobule entirely involved by CIS was signifi-cantly correlated with the presence of an invasive carcinoma; this should thus strongly prompt the pathologist to search for other evidence of invasion. Awareness of these features is an additional, useful tool for reaching a proper diagnosis.

Recommendations for Pathologic Evaluation of Reduction Mammoplasty Specimens: A Prospective Study With Systematic Tissue Sampling.

CONTEXT: - Breast reduction mammaplasty (RMP) for symptomatic macromastia or correction of asymmetry is performed in more than 100 000 patients per year in the United States. The reported incidence of significant pathologic findings (SPF), that is, carcinoma and atypical hyperplasia, ranges from 0.06% to 12.8%. No standard pathology assessment for RMP exists. OBJECTIVES: - To propose standard sampling for microscopic evaluation in RMP specimens, to evaluate the incidence of occult carcinoma and atypical hyperplasia, and to identify clinical risk factors for SPF in patients undergoing RMP. DESIGN: - All RMP specimens from 2006 to 2013 at a single institution were prospectively examined. After baseline gross and microscopic evaluations, each specimen was subjected to systematic additional sampling. The incidence of SPF was tabulated, and variables such as age, specimen weight, previous history of SPF, and results of preoperative mammogram were examined. Clinical follow-up review was also subsequently undertaken. RESULTS: - A total of 595 patients were evaluated. Significant pathologic findings were present in 9.8% (58 of 595) of patients. No cancer was identified in patients younger than 40 years; the rates of carcinoma were 2.4% (14 of 595) in all patients, 3.6% (14 of 392) in patients aged 40 years or older, and 4.3% (10 of 233) in patients aged 50 years or older. No carcinoma or atypical hyperplasia was identified on preoperative mammogram. Increased sampling was associated with a significantly greater frequency of SPF only in patients aged 40 years or older. CONCLUSIONS: - In patients younger than 35 years, gross-only evaluation is sufficient. However, increased sampling may be necessary in patients older than 40 years.

The Pathologic Finding of Combined Lobular Carcinoma In Situ and Invasive Lobular Cancer May Indicate more than Just a High-Risk Marker Role of Lobular Carcinoma In Situ.

For years, lobular carcinoma In Situ (LCIS) has been considered a high-risk marker for developing breast cancer. It is well known that ductal carcinoma In Situ is a precursor for the development of invasive ductal carcinoma, and ductal carcinoma In Situ is reported to be present in invasive ductal carcinoma in at least 40 per cent of cases. A similar relationship between LCIS and invasive lobular carcinoma (ILC) remains in question. This study evaluates the incidence of synchronous LCIS and ILC at our institution. This is a retrospective review of our tumor registry database of women diagnosed with LCIS or ILC from 2000 to 2014. Pathology reports were evaluated to determine the incidence of pure ILC and mixed ILC/LCIS. Those with both LCIS/ILC (mixed group) and those with pure ILC (pure group) were compared for age, surgical intervention, lymph node involvement, tumor size, nuclear grade, and margins between these two groups. A total of 182 women were identified with LCIS, ILC, or mixed LCIS and ILC. There were 76 subjects with pure ILC and 90 with mixed LCIS and ILC. The median and age range for each group were 63.6 (range: 40-97) for the mixed and 64.1 (range: 40-86) for pure groups. Tumor size was evaluated for each group and the median tumor size was 2.5 cm (range: 0.1-7.0cm) for the mixed group and 3.0 cm (range: 0.5-12.5 cm) for the pure group. Nodal involvement was present in 35.23 per cent of the mixed group and 46.3 per cent in the pure group. Surgical treatment for each group was similar, with mastectomy being the preferred surgical option over breast conservation therapy in the mixed and pure groups, 67.07 and 64.71 per cent, respectively. Presently, LCIS is considered a marker, or risk factor, for development of future breast cancer. This retrospective study does identify a strong relationship, 54 per cent, between LCIS and ILC at diagnosis. This high percentage of concurrent LCIS and ILC in surgical/pathological specimens supports the notion that LCIS may in fact have a precursory role in development of invasive lobular carcinoma of the breast. Additional studies to further investigate this relationship between LCIS and ILC, including genomic analysis, are presently underway.

Population-Based Analysis of Breast Cancer Incidence and Survival Outcomes in Women Diagnosed with Lobular Carcinoma In Situ.

PURPOSE: A diagnosis of lobular carcinoma in situ (LCIS) is associated with an increased risk of developing breast cancer, although little data exist on long-term patient outcomes, including those who develop subsequent breast malignancies. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify women with a histological diagnosis of LCIS between 1983 and 2014. The incidence and clinicopathologic features of subsequent malignancies were then examined, and the Kaplan-Meier method and multivariable Cox PH regression used to obtain breast cancer-specific survival (BCSS) estimates and associated hazard ratios. RESULTS: Overall, 19,462 women swith a mean age at LCIS diagnosis of 53.7 years, and a 10- and 20-year cumulative incidence of subsequent breast malignancy of 11.3% [95% confidence interval (CI) 10.7-11.9%] and 19.8% (95% CI 18.8-20.9) met the eligibility criteria. At a median follow-up of 8.1 years (range 0-30.9) a total of 1837 primary breast cancers were diagnosed, of which 55.2% were diagnosed in the ipsilateral breast. Most breast cancers were of low/intermediate grade, hormone receptor-positive, and diagnosed in early stages. Of subsequent malignancies, invasive ductal carcinoma (IDC) distributed equally across both breasts, whereas invasive lobular carcinoma (ILC) was more likely to present in the ipsilateral breast (69.0% ILC vs. 49.2% IDC; p < 0.001). On multivariable analysis, type of surgical treatment for LCIS had no affect on long-term survival (p = 0.44). The 10- and 20-year BCSS for women with LCIS was 98.9 and 96.3%, respectively. CONCLUSION: Women with LCIS who are diagnosed with a subsequent primary breast cancer are often diagnosed in early stages and have excellent BCSS.

Initiation of and adherence to tamoxifen and aromatase inhibitor therapy among elderly women with ductal carcinoma in situ.

BACKGROUND: The National Surgical Adjuvant Breast and Bowel Project B35 and International Breast Cancer Intervention Studies II Ductal Carcinoma In Situ trials showed similar treatment effects of anastrozole and tamoxifen in reducing cancer recurrence risk among ductal carcinoma in situ (DCIS) patients. Studies have shown low levels of hormone therapy drug initiation for DCIS patients, but the current body of literature lacks information on the 5-year adherence rates for these drugs from population-based studies. METHODS: This study evaluated the initiation and 5-year adherence levels for women aged 66 to 85 years who had been diagnosed with estrogen receptor (ER)-positive DCIS between 2007 and 2011 according to the Surveillance, Epidemiology, and End Results and Texas Cancer Registry databases linked to Medicare claims. Chi-square tests, trend tests, and logistic regression were used to identify factors associated with treatment initiation. RESULTS: There were 2871 women with ER-positive DCIS, and approximately 45% began treatment with tamoxifen or aromatase inhibitors (AIs) within 1 year of their DCIS diagnosis. The median age was 73 years for the users and 75 years for the nonusers. Women aged 66 to 70 years who underwent lumpectomy and radiation therapy were significantly more likely to initiate hormone therapy. The initiation of therapy was also significantly associated with patients' geographic location, education, marital status, diagnosis year, and race/ethnicity. Among users, adherence decreased from 67% in the first year to 30% in the fifth year. CONCLUSIONS: Initiation and adherence levels for tamoxifen or AIs among older women with ER-positive DCIS are low. Future studies should develop methods to ensure that informed discussions take place between health care providers and patients regarding hormonal therapy for cancer prevention. Cancer 2017;123:940-47. © 2016 American Cancer Society.

Time-dependent risk of depression, anxiety, and stress-related disorders in patients with invasive and in situ breast cancer.

Despite concerns about the mental health of breast cancer patients, little is known regarding the temporal risk pattern and risk factors of common mental disorders among these patients. We estimated standardized incidence ratios (SIRs) of depression, anxiety and stress-related disorders in a Swedish nationwide cohort of 40,849 women with invasive and 4,402 women with in situ breast cancer (2001-2010, median follow-up = 4.5 years). The impact of patient, tumor and treatment characteristics was analyzed using flexible parametric survival models in a regional cohort of 7,940 invasive breast cancer patients (2001-2013, median follow-up = 7.5 years). Women with invasive breast cancer showed increased rates of depression, anxiety and stress-related disorders [overall SIR (95% CI) = 1.57 (1.46-1.69), 1.55 (1.43-1.68) and 1.77 (1.60-1.95), respectively]. SIRs were highest shortly after diagnosis, but remained increased up to 5 years. Younger age at diagnosis, comorbidity, higher-grade disease, lymph node involvement and chemotherapy were independently associated with the risk of depression and anxiety in invasive cancer patients, with chemotherapy and higher-grade disease conferring short-term risk only, while comorbidities were mainly associated with late-onset events. No clinical risk factors were identified for stress-related disorders except for a greater risk associated with younger age. Patients with in situ cancer only showed an increased incidence of stress-related disorders during the first 6 months after diagnosis [SIR (95% CI) = 2.76 (1.31-5.79)]. The time-dependent risk profile of invasive cancer patients may guide health care professionals for timely and targeted psycho-oncologic interventions.