Timeliness of Breast Diagnostic Imaging and Biopsy in Practice: 15 Years of Collecting, Comparing, and Defining Quality Breast Cancer Care.

BACKGROUND: The literature lacks well-established benchmarks for expected time between screening mammogram to diagnostic imaging and then to core needle breast biopsy. METHODS: Timeliness of diagnostic imaging workup was evaluated using aggregate data from 2005 to 2019 submitted to The National Quality Measures for Breast Centers (NQMBC). RESULTS: A total of 419 breast centers submitted data for 1,805,515 patients on the time from screening mammogram to diagnostic imaging. The overall time was 7 days with 75th, 25th, and 10th percentile values of 5, 10, and 13.5 days, respectively. The average time in business days decreased from 9.1 to 7.1 days (p < 0.001) over the study period with the greatest gains in poorest-performing quartiles. Screening centers and centers in the Midwest had significantly shorter time to diagnostic imaging. Time from diagnostic imaging to core needle biopsy was submitted by 406 facilities representing 386,077 patients. The average time was 6 business days, with 75th, 25th, and 10th percentiles of 4, 9, and 13.7 days, respectively. Time to biopsy improved from a mean of 9.0 to 6.3 days (p < 0.001) with the most improvement in the poorest-performing quartiles. Screening centers, centers in the Midwest, and centers in metropolitan areas had significantly shorter time to biopsy. CONCLUSIONS: In a robust dataset, the time from screening mammogram to diagnostic imaging and from diagnostic imaging to biopsy decreased from 2005 to 2019. On average, patients could expect to have diagnostic imaging and biopsies within 1 week of abnormal results. Monitoring and comparing performance with reported data may improve quality in breast care.

Invasive Lobular Carcinoma-Correlation Between Imaging and Final Pathology: Is MRI Better?

BACKGROUND: Invasive lobular carcinoma (ILC) is associated with high re-excision rates following breast-conserving surgery (BCS). The correlation between lesion size on different imaging modalities and final tumor size has not been well characterized. METHODS: A prospective database of patients with stage I-III breast cancer undergoing BCS between 2006 and 2016 was reviewed. Pearson correlation analysis was used to correlate tumor size on breast imaging to final pathology. RESULTS: Of these, 111 patients with ILC were identified. Mean lesion size was 1.93 cm for MMG, 1.61 cm for US, and 2.51 cm for MRI. Mean tumor size on surgical excision was 2.64 cm. The correlation coefficient between pathology and the different imaging modalities were as follows: MMG .17, US 0.37, and MRI .58. Actual tumor size was underestimated by 1 cm in 27.1% of MMGs, 50% of USs, and in 13.3% of MRIs. 38 patients (34.2%) underwent re-excision. No differences in re-excision rates were noted in patients with and without MRI, 30.3% vs 40.0%, respectively (P = .31). CONCLUSION: While MRI provides a better estimate of tumor size than MMG and US, the size of the tumor on imaging only weakly correlated with pathology. The use of MRI does not decrease re-excision rates.

Flat epithelial atypia on core needle biopsy does not always mandate excisional biopsy.

Flat Epithelia Atypia (FEA) is a proliferative lesion of the breast where cells demonstrate columnar change and cytologic atypia. This lesion has been identified as distinct from the classic atypical hyperplasias (AH). While many patients undergo excisional biopsy, management of FEA identified on core needle biopsy (CNB) is controversial, and the rate of associated ductal carcinoma in situ (DCIS) or invasive cancer is not well defined. The aim of this study was to determine the upstage rate of FEA diagnosed by CNB. We identified patients from a prospectively maintained data base who had FEA diagnosed by CNB from 01/2010 to 07/2015. Patient variables collected included age at presentation, imaging findings, pathologic findings following surgical excision, and subsequent development of breast cancer. Of 132 patients, 62 (n = 62/132, 47.0%) patients had FEA associated with DCIS and invasive ductal carcinoma (IDC) on CNB and were excluded from analysis. Of the remaining 70 patients, median age was 52 (range 31-84) years. Thirty-two (45.7%) patients had FEA plus AH, 4 (5.7%) patients had FEA plus lobular carcinoma in situ (LCIS), and 34 (48.6%) patients had FEA alone or with another non-pathologic finding (pure FEA). Two (6.3%) patients with FEA plus AH had DCIS or IDC on subsequent excisional biopsy. Of the 34 patients with pure FEA who underwent excisional biopsy, only one (2.9%) was found to have IDC. Twenty-two (64.7%) patients with pure FEA who underwent excisional biopsy presented with calcifications on mammography. None of these patients had cancer on excisional biopsy, and 10 (45.5%) patients had AH (3 ADH, 3 ALH, and 4 both ALH and ADH). Twelve (n = 12/34, 35.3%) patients with pure FEA underwent CNB for a mass or asymmetry noted on imaging. Of these 12 patients, 9 (75.0%) had benign findings on excisional biopsy, two (16.7%) patients had AH, and one (8.3%) patient had IDC. Median follow-up was 4.6 years (IQR 3.1-6.5 years). Three (4.3%) patients subsequently developed IDC, two of which were in the contralateral breast. FEA is often found in combination with ADH and ALH as well as carcinoma on CNB. In our study, pure FEA was upstaged to cancer in only 2.9% of patients. Mammographic findings unlikely predict upstaging to malignancy. These findings suggest that excisional biopsy may not be warranted in patients with pure FEA and could be managed with close imaging surveillance.

Outcomes in patients with small node-negative invasive breast cancer.

PURPOSE: There is controversy whether systemic therapy is warranted in patients with small node-negative tumors, especially among those with HER2+ and triple negative breast cancers (TNBC). In this study we sought to compare survival and recurrence rates (RR) in patients with T1mi,a,bN0M0 breast cancer by tumor type. METHODS: Review of a prospectively maintained data base between January 1, 2000 through December 31, 2013 identified 71 patients with HER2+ tumors, 545 with hormone receptor (HR)+ /HER2- tumors, and 45 with TNBC. The three groups were compared with respect to RR, disease-free survival (DFS), and overall survival (OS). Patients with HER2+ disease and TNBC who received chemotherapy were compared to those who did not. RESULTS: At mean follow-up of 4.9 years, the 5-year OS was 95% and 5-year DFS was 98%. RR for HER2+ , HR+ /HER2- , and TNBC was 7.0%, 3.7%, and 4.4% respectively (P = 0.2). There was no significant difference in OS (P = 0.9) and DFS (P = 0.4) amongst the three groups. On multivariable analysis, use of adjuvant chemotherapy was not associated with improvement in DFS or OS. When patients with HER2+ breast cancer and TNBC who received chemotherapy were compared to those who did not, there was no difference in death rates (P = 0.3). CONCLUSIONS: Patients with T1mi,a,bN0M0 invasive breast cancer have an excellent prognosis. The three molecular subtypes differed significantly in age, tumor size, and tumor grade, but had similar RR, DFS, and OS. Chemotherapy was not associated with improved survival. Tumor subtype may not influence recurrence and survival in such small early stage tumors.

Menopausal Status and Outcomes of BRCA Mutation Carriers with Breast Cancer.

Outcomes based on menopausal status of breast cancer (BC) patients who are BRCA mutations carriers (BRCAm) are not well known. A prospective database identified 88 BRCAm with BC from 2005 to 2015. Of the 88 patients, 68 (77.3%) women were premenopausal (Pre-M) and 20 (22.7%) were postmenopausal (Post-M). In the Pre-M group, 52.9 per cent of patients had triple-negative (TN) BC, whereas in the Post-M group, there were more estrogen receptor +(65%; P = 0.129) and less TN (25%; P = 0.041) tumors. Median tumor size was significantly larger in the Pre-M group compared with the Post-M group (P <0.001). Pre-M women were more likely to present with stage III cancers (14.7% vs 0%, respectively, P = 0.082). Ten-year overall survival was 87.9 per cent in the Pre-M group and 93.8 per cent in the Post-M group (P = 0.44), and 25.3 per cent of Pre-M women had recurrences compared with 11.5 per cent of Post-M women (P = 0.24). Premenopausal BRCAm with BC are more likely to have TN, higher stage disease, and twice the number of recurrences at 10 years than Post-M BRCAm. Our study is the first to show worse BC outcomes for Pre-M BRCAm compared with Post-M BRCAm women.

Bilateral Mastectomy as Overtreatment for Breast Cancer in Women Age Forty Years and Younger with Unilateral Operable Invasive Breast Cancer.

BACKGROUND: Young women with breast cancer (BC) have an increased risk of contralateral breast cancer (CBC) compared with older women. This may contribute to the rising rates of bilateral mastectomy (BM), but it is unclear if BM leads to improved outcomes. METHODS: A prospectively maintained database was reviewed. Patient and tumor characteristics, survival, and rate of CBC were compared in women age ≤40 years treated for unilateral Stage 1-3 BC from January 2000 through December 2013. RESULTS: Patients ranged in age from 20 to 40 (mean 36) years. Of the 446 women, 188 had breast conservation surgery (BCS), 78 had unilateral mastectomy (UM), and 183 had BM. UM, BCS, and BM groups did not differ in mean age, tumor type, hormone receptor status, or Her2 status. Patients in the BCS and BM group had smaller, fewer node-positive (p = 0.02) and lower grade tumors (p < 0.01) compared with the UM group. With a median follow-up of 79 months, Disease-free survival was similar for patients treated with BM, BCS (p = 0.22), or UM (p = 0.75). OS was significantly worse in the patients treated with UM (0.02) but was not different between the BCS and BM groups. CBC incidence was 2% (5/263) in patients who underwent BCS or UM, and 0.4% (1/244) in patients without a germline genetic mutation. CONCLUSIONS: BCS and UM resulted in similar disease-free survival (DFS) as BM in patients age 40 years and younger with BC. BCS and BM had similar OS, whereas UM patients had worse OS. Invasive CBC incidence was less than 0.5% at 10 years in patients without identified germline genetic mutations.

Oncological and Surgical Outcomes After Nipple-Sparing Mastectomy: Do Incisions Matter?

BACKGROUND: While nipple-sparing mastectomy (NSM) for the treatment of breast cancer is becoming more accepted, technical aspects are still evolving. Data regarding risk factors contributing to complications after NSM are limited. This study evaluated technical aspects on outcomes of NSM. METHODS: Review of our database identified 201 patients who had NSM during the period from January 2012 to June 2015. We compared the effect of operative techniques on surgical outcomes. RESULTS: A total of 351 NSM were performed in 201 patients. Mean patient age was 47 years. Inframammary (47 %) or periareolar (35 %) incisions were most frequent. Tumescence was used in 203 (58 %) NSM. Skin flaps were created using sharp dissection in 213 (61 %) and electrocautery in 138 (39 %) breasts. Nipple areola complex (NAC) necrosis was seen in 56 (16 %) breasts, of which 7 were severe (2 %). A higher rate of NAC complications was seen with periareolar incisions (p = 0.02). Sharp dissection did not result in significant rates of flap necrosis compared with electrocautery. Ten patients (3 %) had a positive anterior/deep margin, of which 7 (64 %) had an inframammary approach. Twenty-two (11 %) patients had an infection that required intravenous antibiotics. Fourteen (7 %) patients had implant loss. Dissection technique was not associated with implant loss (p = 1.0) or infection (p = 0.84). Forty-two (12 %) patients had radiation and seven (16 %) required implant removal. CONCLUSIONS: NSM has an acceptable complication rate. NAC necrosis requiring excision or implant loss is rare. Postmastectomy radiation is a significant risk factor for implant loss. Inframammary incisions have fewer ischemic complications but may result in tumor-involved margins.

The staging value of sentinel lymph node biopsy for breast cancer: translating pathologic findings to clinical practice.

Axillary nodal status is an important prognostic factor in guiding locoregional and systemic treatment for breast cancer. Sentinel lymph node biopsy (SNB) has revolutionized axillary staging by replacing axillary lymph node dissection (ALND) in node-negative women. Even in select patients whose sentinel lymph nodes (SLNs) contain metastases, SNB alone has become an accepted method of managing the axilla. Identification of micrometastases through immunohistochemical analysis of SLNs that are tumorfree on hematoxylin and eosin staining (H&E) does not confer additional clinical benefit. The use of SNB after neoadjuvant chemotherapy (NAC) remains controversial. In addition to axillary nodal status, tumor biology plays an increasingly important role in guiding therapeutic decisions.

Gene expression signatures of breast cancer stem and progenitor cells do not exhibit features of Warburg metabolism.

INTRODUCTION: Cancers are believed to adapt to continual changes in glucose and oxygen availability by relying almost exclusively on glycolytic metabolism for energy (i.e. the Warburg effect). The process by which breast cancers sustain growth in avascular tissue is thought to be mediated via aberrant hypoxia response with ensuing shifts in glycolytic metabolism. Given their role in initiating and perpetuating tumors, we sought to determine whether breast cancer stem and progenitor cells play an instrumental role in this adaptive metabolic response. METHODS: Breast cancer stem/progenitor cells were isolated from invasive ductal carcinomas, and benign stem cells (SC) were isolated from reduction mammoplasty tissues. Relative expression of 33 genes involved in hypoxia and glucose metabolism was evaluated in flow cytometrically isolated stem and progenitor cell populations. Significance between cohorts and cell populations was determined using Student's 2-tailed t test. RESULTS: While benign stem/progenitor cells exhibited few significant inter-group differences in expression of genes involved in hypoxia regulation or glucose metabolism, breast cancer stem/progenitor cells demonstrated significant inter-group variability. Breast cancer stem/progenitor cells adapted to microenvironments through changes in stem cell numbers and transcription of glycolytic genes. One of four breast cancer stem/progenitor cells subpopulations exhibited an aerobic glycolysis gene expression signature. This subpopulation comprises the majority of the tumor and therefore best reflects invasive ductal carcinoma tumor biology. Although PI3K/AKT mutations are associated with increased proliferation of breast cancer cells, mutations in breast cancer stem/progenitor cells subpopulations did not correlate with changes in metabolic gene expression. CONCLUSIONS: The adaptive capacity of breast cancer stem/progenitor cells may enable tumors to survive variable conditions encountered during progressive stages of cancer growth.

Correlation of breast cancer axillary lymph node metastases with stem cell mutations.

IMPORTANCE: Mutations in oncogenes AKT1, HRAS, and PIK3CA in breast cancers result in abnormal PI3K/Akt signaling and tumor proliferation. They occur in ductal carcinoma in situ, in breast cancers, and in breast cancer stem and progenitor cells (BCSCs). OBJECTIVES: To determine if variability in clinical presentation at diagnosis correlates with PI3K/Akt mutations in BCSCs and provides an early prognostic indicator of increased progression and metastatic potential. DESIGN, SETTING, AND PARTICIPANTS: Malignant (BCSCs) and benign stem cells were collected from fresh surgical specimens via cell sorting and tested for oncogene mutations in a university hospital surgical oncology research laboratory from 30 invasive ductal breast cancers (stages IA through IIIB). MAIN OUTCOMES AND MEASURES: Presence of AKT1, HRAS, and PIK3CA mutations in BCSCs and their correlation with tumor mutations, pathologic tumor stage, tumor histologic grade, tumor hormone receptor status, lymph node metastases, and patient age and condition at the last follow-up contact. RESULTS: Ten tumors had mutations in their BCSCs. In total, 9 tumors with BCSC mutations and 4 tumors with BCSCs without mutations had associated tumor present in the lymph nodes (P = .001). CONCLUSIONS AND RELEVANCE: Tumors in which BCSCs have defects in PI3K/Akt signaling are significantly more likely to manifest nodal metastases. These oncogenic defects may be missed by gross molecular testing of the tumor and are markers of more aggressive breast cancer. Molecular profiling of BCSCs may identify patients who would likely benefit from PI3K/Akt inhibitors, which are being tested in clinical trials.