Explore the vast range of titles available.

MRI is used widely both for screening women who are at increased risk of breast cancer and for treatment selection. Prospective studies confirm that MRI screening of women with known or suspected genetic mutation results in a higher sensitivity for cancer detection than does mammography. However, survival data are not available. In women with breast cancer, MRI detects cancer not identified with other types of screening. In two randomised trials, this increased sensitivity did not translate into improved selection of surgical treatment or a reduction in the number of operations. Data for longer-term outcomes such as ipsilateral breast tumour recurrence rates and contralateral breast cancer incidence are scarce, but to date do not show clear benefit for MRI. MRI is better than other methods of assessing the response to neoadjuvant chemotherapy, and is helpful in identifying the primary tumour in patients who present with axillary adenopathy.

Accurate identification of tumor-derived somatic variants in plasma circulating cell-free DNA (cfDNA) requires understanding of the various biological compartments contributing to the cfDNA pool. We sought to define the technical feasibility of a high-intensity sequencing assay of cfDNA and matched white blood cell DNA covering a large genomic region (508 genes; 2 megabases; >60,000× raw depth) in a prospective study of 124 patients with metastatic cancer, with contemporaneous matched tumor tissue biopsies, and 47 controls without cancer. The assay displayed high sensitivity and specificity, allowing for de novo detection of tumor-derived mutations and inference of tumor mutational burden, microsatellite instability, mutational signatures and sources of somatic mutations identified in cfDNA. The vast majority of cfDNA mutations (81.6% in controls and 53.2% in patients with cancer) had features consistent with clonal hematopoiesis. This cfDNA sequencing approach revealed that clonal hematopoiesis constitutes a pervasive biological phenomenon, emphasizing the importance of matched cfDNA–white blood cell sequencing for accurate variant interpretation. Ultra-sensitive cell-free DNA (cfDNA) sequencing uncovers clonal hematopoiesis as a major source of somatic cfDNA variants in healthy individuals and patients with cancer, and underscores the importance of matched white blood cell DNA sequencing in liquid biopsy procedures.

The role of axillary surgery in the management of breast cancer has changed. Sentinel-lymph-node biopsy is used to identify nodal metastases, but recognition of the lack of therapeutic benefit of this approach, coupled with the emphasis on tumor biology for decisions about systemic therapy, has led to trials examining the elimination of sentinel-lymph-node biopsy in early-stage breast cancer. Two trials involving clinically node-negative patients with breast cancer treated without axillary surgery have now provided outcome data: Reimer et al. present in the Journal results from the INSEMA (Intergroup Sentinel Mamma) trial, 1 and data from the SOUND (Sentinel Node versus Observation . . .

Background The Surgery Versus Active Monitoring for Low-Risk DCIS (LORIS) trial is studying the safety of monitoring core-biopsy diagnosed low-risk ductal carcinoma in situ (DCIS) without excision. We sought to determine the incidence and characteristics of synchronous invasive carcinoma found in LORIS-eligible women who underwent excision, as this knowledge is essential in assessing the safety of observation alone. Methods Women meeting LORIS eligibility criteria (age ≥46 years, screen-detected calcifications, non-high-grade DCIS diagnosed by core biopsy, absence of nipple discharge, or strong family history of breast cancer) who underwent surgical excision from 2009 to 2012 were identified. Histologic findings of excision specimens were reviewed. Results Overall, 296 LORIS-eligible cases were identified; 58 (20 %) had invasive carcinoma on final pathology (90 % invasive ductal, 78 % >1 mm in size, 21 % high grade, 3 % triple negative, 9 % HER2 amplified). Of these, 18 (31 %) were pT1b or larger and 3 (5 %) were pN1. Among eligible upgraded cases, 90 % received radiation, 89 % received endocrine therapy, and 18 % were recommended chemotherapy. Women upgraded to invasive carcinoma were more likely to have intermediate-grade DCIS on core biopsy and to have undergone mastectomy. Conclusions Among LORIS-eligible women, 20 % had invasive carcinoma at surgical excision that was heterogeneous in grade, size, and receptor status. Information gained from surgical excision influenced receipt of adjuvant radiation and endocrine therapy in most patients, and indicated benefit from chemotherapy in 18 % of patients. Surgical excision is warranted until additional risk stratification is available to identify a cohort of DCIS patients at lower risk for clinically significant synchronous invasive carcinoma.

Lobular carcinoma in situ (LCIS) is currently classified as classic (CLCIS), florid (FLCIS), and pleomorphic (PLCIS). Given the rarity of FLCIS and PLCIS, information on their clinico-pathologic features and biologic potential remains limited. We evaluated the upgrade rates at excision of FLCIS and PLCIS diagnosed on inhouse core needle biopsy (CNB) and their clinical presentation and follow-up. Over a period of 11 and a half years, there were a total of 36 inhouse CNBs with pure PLCIS (n = 8), FLCIS (n = 24), or LCIS with pleomorphic features (LCIS-PF) (n = 4). The upgrade rates to invasive carcinoma or ductal carcinoma in situ (DCIS) were 25% for PLCIS (2/8), 17% for FLCIS (4/24), and 0% for LCIS-PF (0/4). The overall upgrade rate of PLCIS and FLCIS combined was 19% (6/32). All but one case (not upgraded at excision) were radiologic–pathologic concordant. Apocrine features, previously reported only in PLCIS, were also noted in FLCIS. HER2 overexpression was seen in 13% of cases. This study highlights the more aggressive biologic features of PLCIS and FLCIS compared to CLCIS and supports surgical management for these lesions.

Triple-negative breast cancer (TNBC) is an operational term that refers to a heterogeneous collection of breast cancers lacking expression of estrogen receptor (ER), progesterone receptor, and HER2. These tumors account for 12–17 % of all breast cancers, preferentially affect young women, are more frequent in women of African and Hispanic descent, and are enriched in the population of patients diagnosed with “interval cancers.” TNBCs account for the majority of breast cancers arising in BRCA1 germline mutation carriers (approximately 80 %), and approximately 11–16 % of all TNBCs harbor BRCA1 or BRCA2 germline mutations. Well-known risk factors for ER-positive cancers, such as reproductive history and hormonal factors, do not appear to have the same correlations for TNBC, and histologic risk factors for TNBC have not been identified. Patients with TNBC have a higher risk of both local and distant recurrence, but this is not mitigated by bigger surgery, and standard criteria should be used to select the approach to local therapy in these patients. Although platinum drugs have shown promise in the treatment of TNBC, standard chemotherapy remains the standard of care outside of a clinical trial.

In recent years, several trials of breast cancer treatment have failed to demonstrate a survival benefit for some previously routine surgical therapies in selected patient groups. As each of these therapeutic approaches has been deemed of low value deimplementation has varied significantly. This demonstrates that effective de-escalation in breast cancer surgery relies on more than the availability of data from randomized controlled trials and other high-quality evidence, but is also influenced by various stakeholders, social expectations, and environmental contexts.

Purpose A joint American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology panel convened to develop a focused update of the American Society of Clinical Oncology guideline concerning use of postmastectomy radiotherapy (PMRT). Methods A recent systematic literature review by Cancer Care Ontario provided the primary evidentiary basis. The joint panel also reviewed targeted literature searches to identify new, potentially practice-changing data. Recommendations The panel unanimously agreed that available evidence shows that PMRT reduces the risks of locoregional failure (LRF), any recurrence, and breast cancer mortality for patients with T1-2 breast cancer with one to three positive axillary nodes. However, some subsets of these patients are likely to have such a low risk of LRF that the absolute benefit of PMRT is outweighed by its potential toxicities. In addition, the acceptable ratio of benefit to toxicity varies among patients and physicians. Thus, the decision to recommend PMRT requires a great deal of clinical judgment. The panel agreed clinicians making such recommendations for individual patients should consider factors that may decrease the risk of LRF, attenuate the benefit of reduced breast cancer-specific mortality, and/or increase risk of complications resulting from PMRT. When clinicians and patients elect to omit axillary dissection after a positive sentinel node biopsy, the panel recommends that these patients receive PMRT only if there is already sufficient information to justify its use without needing to know additional axillary nodes are involved. Patients with axillary nodal involvement after neoadjuvant systemic therapy should receive PMRT. The panel recommends treatment generally be administered to both the internal mammary nodes and the supraclavicular-axillary apical nodes in addition to the chest wall or reconstructed breast.

Metaplastic breast carcinoma (MpBC) is a rare special histologic subtype of breast carcinoma characterized by the presence of squamous and/or mesenchymal differentiation. Most MpBCs are of triple-negative phenotype and neoadjuvant chemotherapy (NAC) is frequently utilized in patients with MpBC. The aim of this study was to evaluate response to NAC in a retrospective cohort of MpBCs. We identified 44 patients with MpBC treated with NAC at our center between 2002 and 2018. Median age was 48 years, 86% were clinical stage II–III, and 36% were clinically node-positive. Most (80%) MpBCs were triple-negative or low (1–10%) hormonal receptor positive and HER2 negative on pre-NAC biopsy. While on NAC, 49% showed no clinical response or clinico-radiological progression. Matrix-producing subtype was associated with clinico-radiological response ( p  = 0.0036). Post NAC, two patients initially ineligible for breast-conserving surgery (BCS) were downstaged to be eligible for BCS, whereas three patients potentially eligible for BCS before treatment became ineligible due to disease progression. Only one (2%) patient had a pathologic complete response (pCR). Among the 16 patients presenting with biopsy-proven clinical node-positive disease, 3 (19%) had nodal pCR. Axillary lymph node dissection was avoided in 3 (19%) patients who had successful axillary downstaging. Residual cancer burden (RCB) was assessed in 22 patients and was significantly associated with disease-free survival and overall survival. We observed a poor response or even disease progression on NAC among patients with MpBC, suggesting that NAC should be reserved for patients with inoperable MpBC.

Some investigators have viewed breast cancer as a local disease that then spreads; others have seen it as a systemic disease from the start. This review argues for another view, since the failure to achieve initial local control allows some tumors to disseminate later, reducing a patient's chance of long-term survival. Recent evidence supports a larger role for aggressive, local therapy for breast cancer. This review argues that initial local control allows some tumors to disseminate later. Recent evidence supports a larger role for aggressive, local therapy for breast cancer. The effect of local therapy on the survival of patients with breast cancer has been debated for decades. Three viewpoints have been proposed on the basis of various hypotheses concerning the biology of breast cancer. Is breast cancer a local disease that spreads predictably over time to develop distant metastases? Is it a systemic disease from the outset, with distant metastases present well before diagnosis? Or is the truth somewhere in between, with many cancers being localized at diagnosis and, if untreated or recurrent, acquiring the ability to metastasize and kill? These differing views have vastly different implications for the . . .