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Perspective on this Article from High Prevalence of Preinvasive Lesions Adjacent to BRCA1/2-Associated Breast Cancers

The role of modified radical mastectomy (MRM) in patients with de novo stage IV inflammatory breast cancer (IBC) remains controversial. We evaluated the impact of MRM on outcomes in this population.Ninety-seven women presenting with stage IV IBC were identified in an institutional database (2007-2016) and were stratified by receipt of MRM or no surgery (non-MRM). Demographic, clinicopathologic, and treatment factors were compared. Local-regional recurrence patterns were described and survival analyses were conducted.All patients initially received chemotherapy. Fifty-two patients (53.6%) underwent MRM; 47 received post-mastectomy radiation. Differences between the non-MRM and MRM groups included tumor receptor subtypes (hormone receptor-positive [HR+]/human epidermal growth factor receptor 2-positive [HER2+]: 4.4% vs. 19.2%; HR+/HER2-negative [HER2-]: 31.1% vs. 44.2%; HR-negative [HR-]/HER2+: 24.4% vs. 15.4%; and HR-/HER2-: 40.0% vs. 21.2%; p = 0.03), number of metastatic sites (3 vs. 2; p = 0.01), and clinical partial/complete response to chemotherapy (13.3% vs. 75.0%; p 0.001). Of the 47 patients who completed trimodality therapy, 6 (12.8%) had a local-regional recurrence. Median overall survival (OS) was 19 months in the non-MRM group and 58 months in the MRM group (p 0.001). On multivariable analysis, clinical N3 disease (hazard ratio 2.16, 95% confidence interval [CI] 1.07-4.37; p = 0.03) as well as tumor subtypes HR+/HER2- (hazard ratio 4.98, 95% CI 1.15-21.47; p = 0.03) and HR-/HER2- (hazard ratio 7.18, 95% CI 1.66-31.07; p = 0.008) were associated with decreased OS. Partial/complete response of distant disease to chemotherapy (hazard ratio 0.43, 95% CI 0.24-0.77; p = 0.005) and receipt of MRM (hazard ratio 0.52, 95% CI 0.29-0.93; p = 0.03) were independently associated with improved OS.In our retrospective study, MRM in de novo stage IV IBC patients is an independent factor associated with improved OS. Our findings strongly support the need for prospective randomized trials evaluating possible survival benefits of MRM in de novo stage IV IBC patients.

Adipose tissue is a dynamic organ that provides endocrine, inflammatory and angiogenic factors, which can assist breast carcinoma cells with invasion and metastasis. Previous studies have shown that adipocytes adjacent to carcinoma, known as cancer-associated adipocytes, undergo extensive changes that correspond to an "activated phenotype," such as reduced size relative to adipocytes in non-neoplastic breast tissue. Optical imaging provides a tool that can be used to characterize adipocyte morphology and other features of the tumor microenvironment. In this study, we used confocal fluorescence microscopy to acquire images of freshly excised breast tissue stained topically with proflavine. We developed a computerized algorithm to identify and quantitatively measure phenotypic properties of adipocytes located adjacent to and far from normal collagen, ductal carcinoma in situ and invasive ductal carcinoma. Adipocytes were measured in confocal fluorescence images of fresh breast tissue collected from 22 patients. Results show that adipocytes adjacent to neoplastic tissue margins have significantly smaller area compared to adipocytes far from the margins of neoplastic lesions and compared to adipocytes adjacent to non-neoplastic collagenous stroma. These findings suggest that confocal microscopic images can be utilized to evaluate phenotypic properties of adipocytes in breast stroma which may be useful in defining alterations in microenvironment that may aid in the development and progression of neoplastic lesions.

The objective of this study was to examine clinical outcomes and patterns of failure in patients with early stage breast cancer who developed an ipsilateral breast tumor recurrence (IBTR) after breast-conserving therapy (BCT) using accelerated partial breast irradiation (APBI).In total, 1440 patients (1449 tumors) with early stage breast cancer who underwent BCT were treated with the MammoSite device to deliver APBI (34 Gray [Gy] in 3.4-Gy fractions). One thousand two hundred fifty-five patients (87%) had invasive breast cancer (IBC) (median tumor size, 10 mm), and 194 patients (13%) had ductal carcinoma in situ (DCIS) (median tumor size, 8 mm). The median follow-up was 60 months.Fifty patients (3.5%) developed an IBTR for a 5-year actuarial rate of 3.61% (3.65% for IBC and 3.36% for DCIS). It was determined that 36 recurrences (72%) represented new primary cancers, and 14 recurrences (28%) represented recurrences of the index lesion. Of the 32 recurrences with known histology, 78% were IBC, and 22% were DCIS. After IBTR, 28 of 38 patients (74%) underwent salvage mastectomy, and 9 of 38 patients (26%) had a second attempt at BCT. Adjuvant therapies included tamoxifen in 8 patients (16%) and systemic chemotherapy in 6 patients (12%). The 3-year rates of disease-free survival, cause-specific survival, and overall survival after IBTR were 58.7%, 92.1%, and 80.5%, respectively.With 5 years of follow-up, APBI produced clinical outcomes and patterns of failure comparable to those achieved with whole breast irradiation. Patients who developed an IBTR after APBI had excellent 3-year survival outcomes after salvage treatments.

Human papillomavirus (HPV) has been proposed as an etiologic agent of breast cancer based on numerous reports of high-risk (oncogenic) HPV types in malignant breast tissues. However, most of those studies used standard and nested solution polymerase chain reaction (PCR) techniques, both of which are disadvantaged by vulnerability to laboratory contamination from positive control DNA and the inability to localize the signal to a specific cell type. To overcome these drawbacks, the authors of this report explored the use of in situ molecular methods of viral detection to reassess the frequency of HPV in malignant breast tissue.In situ hybridization (ISH) was used with probes that were specific for the capsid region of 12 oncogenic HPV types, and in situ PCR (IS-PCR) was used with primers that were specific for the capsid region of HPV-16, which is the most common oncogenic HPV type. These methods were resistant to molecular contamination and allowed identification of the positive cell type. The specimens examined were malignant tissues from patients with 70 breast cancer patients at The University of Texas M. D. Anderson Cancer Center in Houston, Texas.HPV was observed in 4 of 70 specimens (5.7%) using ISH and in 2 of 70 specimens (2.9%) of specimens using IS-PCR. Concordance between the 2 methods was high for negative specimens; both methods yielded negative results in 66 of 70 specimens (94.3%). However, there was no concordance for the few positive specimens, probably because of differences in sensitivity and the targeted HPV types.Oncogenic (high-risk) HPV types were present in malignant breast epithelium very infrequently and, thus, may be causative agents of only a relatively small proportion of all breast cancers.

Tumor cells that disseminate to the bone marrow (disseminated tumor cells [DTCs]) have been identified in 30% of patients with stage I through II breast cancer (BC) and predict outcome. Neoadjuvant chemotherapy (NACT) is effective in reducing the size of primary tumors or eradicating lymph node metastases before surgery, but little is known regarding the presence or significance of DTCs after NACT.The authors evaluated DTCs in 95 patients with clinical stage I through III BC. Bone marrow samples were collected after completion of NACT at the time they underwent surgery for primary BC. DTCs were assessed using an anticytokeratin antibody cocktail. Primary tumor markers, the extent of lymph node (LN) involvement, they type of NACT administered, and response to NACT were compared with presence of DTCs. Chi-square and Fisher exact tests were used for statistical analyses.The median patient age at diagnosis was 51 years, and the median follow-up was 24 months. Forty-six percent of patients had tumors classified as T1/T2, 20% had T3 tumors, 34.5% had T4 tumors, and 81% had lymph node metastasis before NACT. DTCs were identified in 26% of patients after NACT. No associations were observed between DTCs and primary tumor characteristics or LN involvement. A pathologic complete response was observed in 25 patients (26%) but was not predictive of DTCs after NACT (P = .83). DTCs after NACT predicted worse BC-specific survival (P.02).The presence of DTCs was an independent predictor of outcome after NACT. The current results indicated that monitoring hematogenous micrometastatic disease after NACT may be useful in selecting patients who might benefit from additional systemic adjuvant therapies.

Purpose To investigate the impact of histologic type invasive lobular carcinoma (ILC) versus invasive ductal carcinoma (IDC) on response to primary chemotherapy (PC) and long-term outcome. Patients and Methods The study included 1,034 patients with stage II and III breast cancer who participated in six clinical trials of PC at our institution between 1985 and 2002. One hundred twenty-two patients (12%) had ILC and 912 (88%) had IDC. All patients received anthracycline-based PC, and 346 patients (33.5%) also received a taxane as part of PC. Pathologic complete response (pCR) was defined as no evidence of invasive disease in the breast and axillary lymph nodes. Results The median patient age was 48 years (range, 18 to 79 years). Patients with ILC tended to be older (median age, 53 years v 47 years for patients with IDC) and have more hormone-receptor–positive tumors (92% v 62%; P < .001), lower nuclear grade (nuclear grade 3, 16% v 56%; P < .001), and higher stage at diagnosis (10% v 0% with stage IIIB or IIIC disease; P < .001). Patients with ILC were less likely to have a pCR (3% v 15%; P < .001) and had a larger number of involved axillary lymph nodes (41% v 26% had > 3 involved nodes; P = .001). At a median follow-up time of 70 months, ILC patients tended to have longer recurrence-free survival (P = .004) and overall survival (P = .001). Conclusion ILC is characterized by lower rates of pathologic response to PC but better long-term outcomes compared to IDC. pCR might not be a prognostic indicator for this group of patients.

A delayed bilateral pneumothorax complicated unilateral left subclavian vein catheterization and required treatment with tube thoracostomy. This case is unique in the demonstration that bilateral pneumothorax can present in a delayed fashion, and that, as a result of a previously formed pleuropleural fistula, it can occur in patients with a history of noncardiac surgery involving median sternotomy. Historical data on delayed pneumothoraces and bilateral pneumothoraces are presented.