Dataset for pathology reporting of ductal carcinoma in situ, variants of lobular carcinoma in situ and low-grade lesions: recommendations from the International Collaboration on Cancer Reporting (ICCR).

AIMS: To describe a new international dataset for pathology reporting of ductal carcinoma in situ (DCIS), variants of lobular carcinoma in situ (LCIS) and low-grade lesions (encapsulated papillary carcinoma, solid papillary carcinoma in situ, Paget's disease) produced by the International Collaboration on Cancer Reporting (ICCR). METHODS AND RESULTS: The ICCR, a global alliance of pathology bodies, uses a rigorous and efficient process for the development of evidence-based, structured datasets for pathology reporting of common cancers. Their aim is to support quality pathology reporting and engender understanding between the breast surgeon, pathologist, and oncologist for optimal and uniform patient management globally. Here we describe the dataset for DCIS, some variants of LCIS (namely the pleomorphic and the florid variants), and low-grade lesions by a multidisciplinary panel of internationally recognized experts. The agreed dataset comprises 12 core (required) and five noncore (recommended) elements suitable for both developed and low-income jurisdictions, derived from a review of current evidence. Areas of contention were addressed using a pragmatic approach in the absence of evidence. Use of all core elements is the minimum reporting standard for any individual case. Commentary is provided, explaining each element's clinical relevance, definitions to be applied where appropriate for the agreed list of value options and the rationale for considering the element as core or noncore. CONCLUSION: This first internationally agreed dataset for DCIS, variants of LCIS, and low-grade lesions reporting will enable their standardization of pathology reporting and enhance clinicopathological communication leading to improved patient outcomes. Widespread adoption will also facilitate international comparisons, multinational clinical trials, and help to improve the management of breast disease globally.

The TP53 mutation rate differs in breast cancers that arise in women with high or low mammographic density.

Mammographic density (MD) influences breast cancer risk, but how this is mediated is unknown. Molecular differences between breast cancers arising in the context of the lowest and highest quintiles of mammographic density may identify the mechanism through which MD drives breast cancer development. Women diagnosed with invasive or in situ breast cancer where MD measurement was also available (n = 842) were identified from the Lifepool cohort of >54,000 women participating in population-based mammographic screening. This group included 142 carcinomas in the lowest quintile of MD and 119 carcinomas in the highest quintile. Clinico-pathological and family history information were recorded. Tumor DNA was collected where available (n = 56) and sequenced for breast cancer predisposition and driver gene mutations, including copy number alterations. Compared to carcinomas from low-MD breasts, those from high-MD breasts were significantly associated with a younger age at diagnosis and features associated with poor prognosis. Low- and high-MD carcinomas matched for grade, histological subtype, and hormone receptor status were compared for somatic genetic features. Low-MD carcinomas had a significantly increased frequency of TP53 mutations, higher homologous recombination deficiency, higher fraction of the genome altered, and more copy number gains on chromosome 1q and losses on 17p. While high-MD carcinomas showed enrichment of tumor-infiltrating lymphocytes in the stroma. The data demonstrate that when tumors were matched for confounding clinico-pathological features, a proportion in the lowest quintile of MD appear biologically distinct, reflective of microenvironment differences between the lowest and highest quintiles of MD.

Treatment Intensity Differences After Early-Stage Breast Cancer (ESBC) Diagnosis Depending on Participation in a Screening Program.

BACKGROUND: While population mammographic screening identifies early-stage breast cancers (ESBCs; ductal carcinoma in situ [DCIS] and invasive disease stages 1-3A), commentaries suggest that harms from overdiagnosis and overtreatment may outweigh the benefits. Apparent benefits to patients with screen-detected cancers may be due to selection bias from exclusion of interval cancers (ICs). Treatment intensity is rarely discussed, with an assumption that all ESBCs are treated similarly. We hypothesized that women diagnosed while in a screening program would receive less-intense treatment than those never or not recently screened (NRS). METHODS: This was a retrospective analysis of all women aged 50-69 years managed for ESBC (invasive or DCIS) during the period 2007-2013 within a single service, comparing treatment according to screening status. Data on demographics, detection, pathology, and treatment were derived from hospital, cancer registry, and screening service records. RESULTS: Overall, 622 patients were active screeners (AS) at diagnosis (569 screen-detected and 53 ICs) and 169 patients were NRS. AS cancers were smaller (17 mm vs. 26 mm, p < 0.0001), less likely to involve nodes (26% vs. 48%, p < 0.0001), and lower grade. For invasive cancer, NRS patients were more likely to be recommended for mastectomies [35% vs. 16%; risk ratio(RR) 2.2, p < 0.0001], axillary dissection (43% vs. 19%; RR 2.3, p < 0.0001), adjuvant chemotherapy (65% vs. 37%; RR 1.7, p < 0.0001), and postmastectomy radiotherapy (58% vs. 39%; RR 1.5, p = 0.04). CONCLUSION: Participants in population screening diagnosed with ESBC receive substantially less-intense treatment than non-participants. Differences persist when potential overdiagnosis is taken into account; these differences should be factored into debates around mammographic screening.

Selective use of whole breast radiotherapy after breast conserving surgery for invasive breast cancer and DCIS.

BACKGROUND: Radiotherapy following breast conservation is routine in the treatment of invasive breast cancer and is commonly used in ductal carcinoma in situ to decrease local recurrence. However, adjuvant breast radiotherapy has significant short and longer-term side effects and consumes substantial health care resources. We aimed to review the randomised controlled trials and attempted to identify clinico-pathological factors and molecular markers associated with the risk of local recurrence. METHODS: A literature search using the Medline and Ovid databases between 1965 and 2011 was conducted using the terms 'breast conservation' and radiotherapy, and radiotherapy and DCIS. Only papers with randomised clinical trials published in English in adult were included. Only Level 2 evidence and above was included. RESULTS: Three meta-analyses and 17 randomised controlled trials have been published in invasive disease and one meta-analysis and four randomised controlled trials for DCIS. Overall, adjuvant radiotherapy provides a 15.7% decrease in local recurrence and 3.8% decrease in 15-year risk of breast cancer death. The key clinico-pathological factors, which enable stratification into high, intermediate or low risk groups include age, oestrogen receptor positivity, use of tamoxifen and extent of surgery. Absolute reductions in 15-year risk of breast cancer death in these three prediction categories are 7.8%, 1.1%, and 0.1% respectively Adjuvant radiotherapy provides a 60% risk reduction in local recurrence in DCIS with no impact on distal metastases or overall survival. Size, pathological subtype and margins are major risk factors for local recurrence in DCIS. CONCLUSIONS: Adjuvant radiotherapy consistently decreases local recurrence across all subtypes of invasive and in-situ disease. While it has a survival advantage in those with invasive disease, this is not seen with DCIS and is minimal in invasive disease where the risk of local recurrence is low. This group includes women over 70 with node negative, ER positive tumours<2 cm.

Does immediate breast reconstruction compromise the delivery of adjuvant chemotherapy?

BACKGROUND: Immediate breast reconstruction (IBR) provides psychological benefit to many early breast cancer patients however concerns persist regarding its potential impact on chemotherapy delivery. We investigated the association between IBR, complications and adjuvant chemotherapy delivery. METHOD: Retrospective analysis of patients in an academic breast service, who underwent mastectomy, with or without reconstruction, and received adjuvant chemotherapy. RESULTS: Comparisons were made between 107 patients who received IBR and 113 who received mastectomy alone. Those receiving IBR were on average younger, with lower body mass index (BMI) and better prognoses. Overall complication rates were comparable (mastectomy alone: 45.1% versus IBR: 35.5%, p = 0.2). There was more return to surgery in the IBR group with 11.5% of tissue expanders requiring removal, whilst more seromas occurred in the mastectomy group. There was no significant difference in the median time to chemotherapy. CONCLUSION: We found no evidence that IBR compromised the delivery of adjuvant chemotherapy, although there was a significant incidence of implant infection.