Progressive polarity loss and luminal collapse disrupt tissue organization in carcinoma.

Epithelial cancers (carcinoma) account for 80%-90% of all cancers. The development of carcinoma is associated with disrupted epithelial organization and solid ductal structures. The mechanisms underlying the morphological development of carcinoma are poorly understood, but it is thought that loss of cell polarity is an early event. Here we report the characterization of the development of human breast lesions leading to carcinoma. We identified a unique mechanism that generates solid ducts in carcinoma through progressive loss of polarity and collapse of the luminal architecture. This program initiates with asymmetric divisions of polarized cells that generate a stratified epithelium containing both polarized and depolarized cells. Stratified regions form cords that penetrate into the lumen, subdividing it into polarized secondary lumina. The secondary lumina then collapse with a concomitant decrease in RhoA and myosin II activity at the apical membrane and ultimately lose apical-basal polarity. By restoring RhoA activity in mice, ducts maintained lumen and cell polarity. Notably, disrupted tissue architecture through luminal collapse was reversible, and ducts with a lumen were re-established after oncogene suppression in vivo. This reveals a novel and common mechanism that contributes to carcinoma development by progressively disrupting cell and tissue organization.

Preoperative factors that predict pathologic nodal involvement in early-stage HER2+ breast cancer: selecting cT1cN0 patients for treatment with neoadjuvant chemotherapy versus upfront surgery.

PURPOSE: The goal of this study was to identify the preoperative predictors of pathologic nodal metastases (pN+) in cT1cN0 HER2+ breast cancer undergoing upfront surgery. METHODS: We retrospectively reviewed data from women with cT1-T2N0 HER2+ breast cancer treated with neoadjuvant therapy (NAC) or upfront surgery at our institution between 2012 and 2023. Factors associated with management strategy were evaluated, and in those undergoing upfront surgery, univariate analyses were performed to identify the clinicopathologic factors associated with nodal metastases. RESULTS: Overall, 255 women with cT1-T2N0 HER2+ breast cancer met inclusion criteria, including 170 (68.6%) upfront surgery patients and 85 (31.4%) who underwent NAC. The median age at diagnosis was 59 years (range, 27-90 years). Younger age, larger clinical tumor size, high-grade disease, ER-PR-HER2+ subtype, and year of diagnosis after 2019 were significantly associated with receipt of NAC (p < 0.05). In those undergoing upfront surgery, 25.3% were pN+ , including 32.5% of cT1cN0 tumors. Factors associated with nodal involvement included age under 50, larger clinical tumor size, lymphovascular invasion (LVI), multifocality/multicentricity, and abnormal lymph nodes on axillary ultrasound (p < 0.05). In subset analysis of cT1cN0 HER2+ cases, LVI remained the strongest predictor of pN + disease (73.3% vs. 22.6%, p < 0.001). Patients with cT1cN0 HER2+ breast cancer under 50 years had a 47.1% likelihood of pN+ disease. CONCLUSION: Patients with cT1cN0 breast cancer have a 32.5% likelihood of nodal metastases, with higher incidence with younger age, LVI, multifocality/multicentricity, and abnormal axillary ultrasound. The presence of these factors may identify the patients who would benefit from treatment with neoadjuvant chemotherapy.

Impact of Margin Status on Local Recurrence in Patients with Breast Cancer Undergoing Breast-Conserving Surgery After Neoadjuvant Chemotherapy: A Retrospective Multi-Institutional Cohort Study.

BACKGROUND: Questions have been raised as to an increased risk of local recurrence with breast-conserving surgery (BCS) post NAC highlighting the uncertainty around optimal margin width in this patient population. We examined the association between margin status and local recurrence-free survival (LRFS) in patients who underwent BCS following NAC. METHODS: We performed a retrospective cohort study of adult female patients with stage I-III breast cancer who underwent NAC followed by BCS between 2012 and 2021 at two cancer centers. Margins were categorized as "close" if they were < 1 mm. RESULTS: The full cohort included 544 patients with a median age of 53 years (interquartile range [IQR] 44-64). Pathologic complete response (pCR) was achieved in 41.2% of the overall cohort (n = 224). Of the 320 with residual disease, 29.4% (n = 94) had at least one close margin, and 10.9% (n = 35) had ≥2 close margins. Median follow-up was 55 months (IQR 32-83); 4.8% had an ipsilateral breast recurrence (n = 26). Patients with pCR had a higher 5-year LRFS than those with residual disease (98.0% vs. 91.6%, p = 0.02). There was no difference in 5-year LRFS between the margin categories (clear vs. 1 close margin vs. ≥2 close margins) in those with residual disease (92.2% vs. 88.9% vs. 92.9%) (p = 0.78). CONCLUSIONS: In patients undergoing BCS post-NAC, those who achieved pCR had a significantly higher LRFS compared with those with residual disease at the time of surgery, but LRFS was not associated with margin width nor the number of close margins.

Surgical Decision Making in Genetically High-Risk Women: Quantifying Postoperative Complications and Long-Term Risks of Supplemental Surgery After Risk-Reducing Mastectomy.

BACKGROUND: Risk-reducing mastectomy (RRM) helps prevent breast cancer in high-risk women but also carries a risk of unanticipated supplemental surgeries. We sought to determine the likelihood of supplemental surgeries following RRM. METHODS: We performed a retrospective cohort study of female patients with a confirmed germline pathogenic variant (GPV) in a breast cancer susceptibility gene (BRCA1/2, PALB2 and others) who underwent bilateral or contralateral RRM at our institution between 2006 and 2022. Supplemental surgeries were defined as any operation requiring general or local anesthesia performed outside of the initially planned procedure(s). The Kaplan-Meier method was used to estimate the 5-years cumulative incidence of supplemental surgery. RESULTS: Of 560 GPV carriers, RRMs were performed in 258 (46.1%) women. The median age of the cohort was 44 years (interquartile range 37-52 years), with 33 (12.8%) patients undergoing RRM without reconstruction and 225 (87.2%) undergoing RRM with reconstruction. Following surgery, 34 patients (13.2%) developed early (< 30 days) postoperative complications, including infection, hematoma, seroma, loss of the nipple areola complex, flap necrosis, implant exposure and/or prosthesis removal. At a median follow-up of 3.8 years, 94 (36.4%) GPV carriers underwent at least one reoperation. Participants who experienced an early postoperative complication had the highest rate of reoperation (85.3% vs. 29.0%; p < 0.001) and a significantly higher likelihood of multiple additional surgical interventions (41.2% vs. 10.7%; p < 0.001). The 5-years rate of supplemental surgery was 39.2% [95% confidence interval (CI) 32.7-46.5] in the overall cohort and 31.5% (95% CI 24.9-39.3) in patients without an early postoperative complication. CONCLUSIONS: Unanticipated supplemental surgeries occur in 40% of GPV carriers following RRM and in nearly one-third of patients without early postoperative complications.

Opioid prescribing practices in breast oncologic surgery-A retrospective cohort study.

BACKGROUND: In breast oncologic surgery, 75% of patients receive a postoperative opioid prescription at discharge, and 10%-20% will develop persistent opioid use. To inform future institutional guidelines, the objective of this study was to determine baseline opioid prescribing patterns in a single high-volume, referral-based breast center. We hypothesized that opioid prescribing practices varied between procedures and operating surgeons. METHODS: A retrospective analysis of all women undergoing breast cancer surgery between January and December 2019. Opioid prescriptions at discharge were converted to morphine milligram equivalents (MME). The primary outcome of interest was MME prescribed at discharge. Multiple linear regression was used to identify factors independently associated with MME prescribed. RESULTS: 392 patients met inclusion criteria; 68.3% underwent partial mastectomy. Median age was 61 (interquartile range [IQR] 51-70). Median MME prescribed at discharge was 112.5 (IQR 75-150); 83.9% of patients were prescribed co-analgesia. The prescriber was a trainee in 37.7% of cases. 15 patients (3.8%) required opioid renewal. On multivariate analysis, axillary procedure was associated with increased MME (ß = 17, 95% CI 5.5-28 and ß = 32, 95% CI 17-47, for sentinel node and axillary dissection, respectively). However, the factor with the greatest impact on MME was operating surgeon (ß = 72, 95% CI 58-87). Residents prescribed less MME compared to attending surgeons (ß = 11, 95% CI -22; -0.06). CONCLUSION: In a tertiary care center, the operating surgeon had the greatest influence on opioid prescribing practices, and trainees tended to prescribe less MME. These findings support the need for a standardized approach to optimize prescribing and reduce opioid-related harms after oncologic breast surgery.

Margin Status and Local Recurrence in Phyllodes Tumours of the Breast: A Canadian Series.

BACKGROUND: Phyllodes tumours of the breast are rare fibroepithelial neoplasms with a propensity for recurrence. While surgical excision remains the standard of care, the optimal margin width is an area of active investigation. Recent studies have questioned the necessity for wide, local excision. METHODS: We conducted a retrospective, cohort study of patients with phyllodes tumours treated at our institution between 2003 and 2021. Demographic, histopathological, and recurrence data were captured; malignant phyllodes were excluded. Cox proportional hazard models were used to identify covariates associated with local recurrence. RESULTS: Of 187 patients with phyllodes tumours, 82.9% (n = 155) were classified as benign while 17.1% (n = 32) were borderline. Initial surgical margins were positive in 26.2% (n = 49), < 2 mm in 50.8% (n = 95), and ≥ 2 mm in 23% (n = 43) patients. Among patients with positive margins, 61.2% (n = 30) underwent margin revision. At a median follow-up of 2.9 years, the recurrence rate was 3.7%. On univariate analysis, only a positive margin at the time of initial surgery and not margin width was significantly associated with a higher rate of disease recurrence (hazard ratio [HR] 9.52, 95% confidence interval [CI] 1.85-49.2), as was a size greater than 4 cm on preoperative imaging (HR 10.78, 95% CI 0.97-120.1). Revision of an initially positive margin was not significantly associated with decreased local recurrence (p = 1). CONCLUSIONS: In this large cohort of benign and borderline phyllodes tumours, positive resection margins and not margin width at the initial surgery were associated with a increased recurrence. Individualization of decisions regarding margin reexcision is important.

Multicenter Adoption and Outcomes of Nodal Observation for Patients with Melanoma and Sentinel Lymph Node Metastases.

BACKGROUND: Following publication of the MSLT-II trial showing no survival benefit of completion lymphadenectomy (CLND) in patients with melanoma sentinel lymph node (SLN) metastases, it is expected that practice patterns have changed. The purpose of this study is to understand real-world practices and outcomes after publication of this landmark trial. PATIENTS AND METHODS: Patients with truncal/extremity melanoma SLN metastases diagnosed between 2013 and 2019 at four academic cancer centers were included in this retrospective cohort study. Descriptive statistics, Cox proportional hazards model, and multivariable regression were used to characterize the cohort and identify predictors of CLND, harboring non-SLN (NSLN) metastases, and survival. RESULTS: Results of 1176 patients undergoing SLN biopsy, 183 had SLN metastases. The number of patients who underwent CLND before versus after trial publication was 75.7.% versus 20.5% (HR 0.16, 95% CI 0.09-0.28). Of those undergoing nodal observation (NO), 92% had a first nodal-basin ultrasound, while 63% of patients had a fourth. In exploratory multivariable analyses, age ≥ 50 years was associated with lower rate of CLND (HR 0.58, 95% CI 0.36-0.92) and larger SLN deposit (> 1.0 mm) with increased rate of CLND (HR 1.87, 95% CI 1.17-3.00) in the complete cohort. Extracapsular extension was associated with increased risk of NSLN metastases (HR 12.43, 95% CI 2.48-62.31). Adjusted survival analysis demonstrated no difference in recurrence or mortality between patients treated with CLND versus NO at median 2.2-year follow-up. CONCLUSION: Nodal observation was rapidly adopted into practice in patients with melanoma SLN metastases at four centers in Canada. Younger age and higher nodal burden were associated with increased use of CLND after trial publication. Ultrasound (US) surveillance decreased with time from SLNB. In our study, CLND was not associated with a decreased risk of recurrence or mortality.

Incidence of Occult Breast Cancer in Carriers of BRCA1/2 or Other High-Penetrance Pathogenic Variants Undergoing Prophylactic Mastectomy: When is Sentinel Lymph Node Biopsy Indicated?

BACKGROUND: This study sought to determine the likelihood of occult malignancy during risk-reducing mastectomy in high-penetrance pathogenic variant carriers to help refine axillary staging recommendations. METHODS: The authors performed a retrospective cohort study analyzing all female carriers of pathogenic variants in BRCA1/2, PALB2 or other genes who underwent prophylactic surgery at their institution between 2006 and 2021. Occult breast cancer was defined as the unanticipated presence of in situ or invasive malignancy on pathologic evaluation of prophylactic mastectomy specimens. RESULTS: Of 523 women, 243 carriers met the inclusion criteria for the study including 124 BRCA1 (51.0%), 108 BRCA2 (44.4%), and 11 PALB2, TP53, CDH1, or PTEN (4.6%) carriers. The median age was 44 years (interquartile range, 37-52 years). Overall, 128 women (52.7%) underwent bilateral prophylactic mastectomies, and 115 (47.3%) underwent contralateral prophylactic mastectomy. In the 371 mastectomies performed, 16 (4.3%) occult malignancies were diagnosed. Most of the occult malignancies were ductal carcinoma in situ (13 mastectomies, 3.5%), whereas 3 mastectomies (0.8%) contained invasive breast cancer. If Breast Imaging Reporting and Data System (BIRADS) 1-2 or BIRADS 3 findings were reported on preoperative magnetic resonance imaging (MRI), the rate of occult malignancy decreased to 3.0 and 2.8%, respectively, per mastectomy. The patient-level factors associated with a likelihood of occult breast cancer greater than 10% included a history of prior breast cancer, age exceeding 60 years, and BIRADS 4 findings on preoperative imaging. CONCLUSIONS: Occult invasive malignancy was detected in less than 1% of the risk-reducing mastectomies performed for women with BRCA1/2 or PALB2 pathogenic variants. Sentinel lymph node biopsy can be safely avoided when BIRADS 1-3 findings are reported on preoperative MRI.

Infiltration of CD8+ T cells into tumor cell clusters in triple-negative breast cancer.

Infiltration of [Formula: see text] T lymphocytes into solid tumors is associated with good prognosis in various types of cancer, including triple-negative breast cancer (TNBC). However, the mechanisms underlying different infiltration levels are largely unknown. Here, we have characterized the spatial profile of [Formula: see text] T cells around tumor cell clusters (tightly connected tumor cells) in the core and margin regions in TNBC patient samples. We found that in some patients, the [Formula: see text] T cell density first decreases when moving in from the boundary of the tumor cell clusters and then rises again when approaching the center. To explain various infiltration profiles, we modeled the dynamics of T cell density via partial differential equations. We spatially modulated the diffusion/chemotactic coefficients of T cells (to mimic physical barriers) or introduced the localized secretion of a diffusing T cell chemorepellent. Combining the spatial-profile analysis and the modeling led to support for the second idea; i.e., there exists a possible chemorepellent inside tumor cell clusters, which prevents [Formula: see text] T cells from infiltrating into tumor cell clusters. This conclusion was consistent with an investigation into the properties of collagen fibers which suggested that variations in desmoplastic elements does not limit infiltration of [Formula: see text] T lymphocytes, as we did not observe significant correlations between the level of T cell infiltration and fiber properties. Our work provides evidence that [Formula: see text] T cells can cross typical fibrotic barriers and thus their infiltration into tumor clusters is governed by other mechanisms possibly involving a local repellent.

Dynamic Neutrophil-to-Lymphocyte Ratio: A Novel Prognosis Measure for Triple-Negative Breast Cancer.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) is a measure of systemic inflammation and a prognostic factor for multiple malignancies. This study assesses the value of the NLR as an independent prognostic marker in triple-negative breast cancer (TNBC) and explores the association between dynamic NLR changes and patient outcomes. METHODS: The study retrospectively analyzed a prospectively maintained database including patients 18 to 80 years old with TNBC treated at the authors' institution between 2006 to 2016. Clinical and demographic data were collected, including blood test results and treatments received. Age at diagnosis, stage of disease, and NLR scores were tested for association with overall and disease-free survival in uni- and multivariate Cox models. RESULTS: The inclusion criteria were met by 329 women with a median age of 58. Most of the patients had early-stage disease (30.1% with stage 1 and 47% with stage 2 malignancy). An NLR higher than 2.84 at diagnosis was associated with decreased overall survival (hazard ratio [HR], 1.8; 95% confidence interval [CI], 1.023-3.176), whereas an NLR higher than 7.82 at any time during the follow-up period was a strong predictor of 5-year mortality (HR, 10.76; 95% CI, 4.193-26.58), independent of age or stage of disease. Patients who experienced recurrence had a higher NLR than their counterparts during the 6 months before recurrence. The NLR also significantly rose during the final 18 months of life (p < 0.01). CONCLUSION: The NLR is an important prognostic marker in TNBC, both at diagnosis and during the course of the disease. Moreover, dynamic changes in NLR strongly correlate with disease recurrence and the time of death.

Analysis of incidence, mortality trends, and geographic distribution of breast cancer patients in Canada.

BACKGROUND/PURPOSE: Breast cancer is the malignancy with the highest incidence rate excluding non-melanoma skin cancers, and the second leading cause of cancer-related deaths among Canadian women. Many modifiable risk factors have been linked to the pathogenesis of this disease. The purpose of this study is to analyze the epidemiology of breast cancer in Canada and to examine its geographic distribution to help identify new risk factors for this disease. METHODS: Three independent population-based cancer registries were used to retrospectively analyze demographic data from Canadian women diagnosed with invasive breast cancer across all provinces and territories between 1992 and 2010. The incidence and mortality rates were assessed at the provincial, city, and forward sortation area (FSA) postal code levels. RESULTS: The overall age-adjusted incidence rate was 114.4 cases per 100,000 females per year. Six provinces and several groups of FSAs had significantly higher incidence rates. There was a significant increase in incidence and decrease in mortality rates between 1992 and 2010. The overall mortality rate was 31.5 deaths per 100,000 females per year. However, three provinces had significantly higher mortality rates. CONCLUSION: By identifying high-incidence areas for breast cancer, our study will help identify patient populations that are at higher risk for this malignancy. It will also act as a foundation for future studies to establish novel risk factors for this disease.

A mixed-methods evaluation of a community physical activity program for breast cancer survivors.

BACKGROUND: Given the benefits of physical activity for health and survival, clinicians are seeking opportunities for cancer patients to become more active independent of rehabilitation programs that are small, time-limited, and location specific. This proof-of-concept study evaluated a community-based physical activity program (Curves™) for increasing physical activity among women diagnosed and treated for breast cancer. METHODS: Women were recruited from a breast cancer clinic through physician chart review. In study 1, women (n = 14) received the community physical activity memberships (Curves™), guidelines, and a pedometer. This group was compared to women (n = 16) who received physical activity guidelines and a pedometer on changes in physical activity. In study 2, women (n = 66) completed self-report questionnaires after Curves™ memberships expired to evaluate the program. Study 3 was a qualitative study exploring the benefits and barriers of the physical activity program among women (n = 6) who attended Curves™ regularly. RESULTS: Provision of memberships to a community-based physical activity program did not improve physical activity levels beyond educational and information resources. However, there are a number of advantages to community-based physical activity programs, and the women offer a number of suggestions for improvements for community physical activity opportunities aimed at breast cancer survivors. CONCLUSIONS: Women-only community-based physical activity programs may be a viable option to help introduce women to get active after treatment. Trial registration ISRCTN, ISRCTN14747810. Registered on 18 October 2017-Retrospectively registered, https://doi.org/10.1186/ISRCTN14747810.

Axillary Lymph Node Ultrasound Following Neoadjuvant Chemotherapy in Biopsy-Proven Node-Positive Breast Cancer: Results from the SN FNAC Study.

BACKGROUND: The sentinel node biopsy following neoadjuvant chemotherapy (SN FNAC) study has shown that in node-positive (N+) breast cancer, sentinel node biopsy (SNB) can be performed following neoadjuvant chemotherapy (NAC), with a low false negative rate (FNR = 8.4%). A secondary endpoint of the SN FNAC study was to determine whether axillary ultrasound (AxUS) could predict axillary pathological complete response (ypN0) and increase the accuracy of SNB. METHODS: The SN FNAC trial is a study of patients with biopsy-proven N+ breast cancer who underwent SNB followed by completion node dissection. All patients had AxUS following NAC and the axillary nodes were classified as either positive (AxUS+) or negative (AxUS-). AxUS was compared with the final axillary pathology results. RESULTS: There was no statistical difference in the baseline characteristics of patients with AxUS+ versus those with AxUS-. Overall, 82.5% (47/57) of AxUS+ patients had residual positive lymph nodes (ypN+) at surgery and 53.8% (42/78) of AxUS- patients had ypN+. Post NAC AxUS sensitivity was 52.8%, specificity 78.3%, and negative predictive value 46.2%. AxUS FNR was 47.2%, versus 8.4% for SNB. If post-NAC AxUS- was used to select patients for SNB, FNR would decrease from 8.4 to 2.7%. However, using post-NAC AxUS in addition to SNB as an indication for ALND would have led to unnecessary ALND in 7.8% of all patients. CONCLUSION: AxUS is not appropriate as a standalone staging procedure, and SNB itself is sufficient to assess the axilla post NAC in patients who present with N+ breast cancer.

MRI Performance in Detecting pCR After Neoadjuvant Chemotherapy by Molecular Subtype of Breast Cancer.

BACKGROUND: MRI performance in detecting pathologic complete response (pCR) post-neoadjuvant chemotherapy (NAC) in breast cancer has been previously explored. However, since tumor response varies by molecular subtype, it is plausible that imaging performance also varies. Therefore, we performed a literature review on subtype-specific MRI performance in detecting pCR post-NAC. METHODS: Two reviewers searched Cochrane, PubMed, and EMBASE for articles published between 2013 and 2018 that examined MRI performance in detecting pCR post-NAC. After filtering, ten primary research articles were included. Statistical metrics, such as sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), were extracted per study for triple negative, HR+/HER2-, and HER2+ patients. RESULTS: Ten studies involving 2310 patients were included. In triple negative breast cancer, MRI showed NPV (58-100%) and PPV (72.7-94.7%) across 446 patients and sensitivity (45.5-100%) and specificity (49-94.4%) in 375 patients. In HR+/HER2- breast cancer patients, MRI showed NPV (29.4-100%) and PPV (21.4-95.1%) across 851 patients and sensitivity (43-100%) and specificity (45-93%) across 780 patients. In HER2+-enriched subtype, MRI showed NPV (62-94.6%) and PPV (34.9-72%) in 243 patients and sensitivity (36.2-83%) and specificity (47-90%) in 255 patients. CONCLUSION: MRI accuracy in detecting pCR post-NAC by subtype is not as consistent, nor as high, as individual studies suggest. Larger studies using standardized pCR definition with appropriate timing of surgery and MRI need to be conducted. This study has shown that MRI is in fact not an accurate prediction of pCR, and thus, clinicians may need to rely on other approaches such as biopsies of the tumor bed.

Atypical ductal hyperplasia diagnosed at sonographically guided core needle biopsy: frequency, final surgical outcome, and factors associated with underestimation.

OBJECTIVE: The purposes of this article were to review the mammographic and sonographic features of breast masses yielding atypical ductal hyperplasia (ADH) at sonographically guided biopsy, evaluate the surgical pathology outcome of these lesions, and determine whether clinical or imaging features can be used to predict upgrade to malignancy. MATERIALS AND METHODS: Among 6325 sonographically guided biopsies (2003- 2010) (14-gauge cores), 56 yielded the diagnosis of ADH (0.9%). Six patients were excluded (lost to follow-up). Fifty lesions were surgically excised in 45 patients. Mammographic and sonographic features were analyzed in consensus by two radiologists using the BI-RADS lexicon. RESULTS: Forty-five patients (mean age, 56 years; 12 < 50 years; six with synchronous breast carcinoma) had 50 ADH lesions (median size, 0.6 cm). Surgical excision yielded malignancy in 28 cases (56% underestimation rate). Among 42 mammograms (47 lesions), 30 lesions were identified (30/47, 64%) as masses (12/30, 40%), asymmetric densities (10/30, 33%), microcalcifications (4/30, 13%), and architectural distortions (4/30, 13%). Sonographically, most lesions appeared as hypoechoic masses (64%, 30/47) with irregular shape (51%, 24/47), microlobulated margins (49%, 23/47), no posterior acoustic feature (25/47, 53%), abrupt interface (70%, 33/47), and parallel orientation (57%, 27/47). No mammographic and sonographic features were associated with malignant outcome, whereas age less than 50 years (p = 0.03) and synchronous malignancy (p = 0.03) were associated with malignant outcome. CONCLUSION: ADH diagnosed at sonographically guided 14-gauge core needle biopsy shows a high underestimation rate. Synchronous carcinoma or age less than 50 years is associated with malignant outcome.

Adherence to anti-estrogen therapy in seniors with breast cancer: how well are we doing?

A third of breast cancers (BC) occur in women ≥65 years (seniors). Anti-estrogen therapy (AET) significantly reduces BC recurrence and death. This study characterizes determinants of adherence to AET in seniors with BC. Provincial cancer registry and administrative claims data were accessed for all non-metastatic BC diagnosed in Quebec (1998-2005) to identify seniors treated for 5 years with AET. Multivariate linear regression was used to assess the association with patient, disease, and physician characteristics and the 5-year medication possession ratio (MPR) for each patient. 4,715 women were included (mean age: 72.9). Mean MPR was 83.5%, 79% of patients reached a 5-year MPR of ≥80%, and 34% discontinued AET at some point during treatment. The cumulative probability of discontinuation was 33.8% (mean time to discontinuation 2.3 years). The MPR decreased with increasing age and non-BC related hospitalizations, p < 0.05. Each new medication added during the 5-years decreased the MPR by 0.3% (p < 0.05). Women with in situ disease, on antidepressants at baseline, or treated with Tamoxifen had a lower MPR by 6.5% (p = 0.0002), 4.7% (p = 0.003) and 6% (p = 0.001), respectively. Switching AET type was associated with a lower MPR by 5.3% (p = 0.002) if the switch occurred during the first year. Optimal 5-year adherence to AET in seniors with BC remained a challenge and medication discontinuation rates were high. Advanced age, increasing number of hospitalizations, in situ disease, baseline use of antidepressants, Tamoxifen (versus aromatase inhibitors), early switches of AET type, and newly added medications significantly reduced the MPR.

Compression-refractory breast hematoma secondary to pseudoaneurysm after stereotactically guided vacuum-assisted biopsy: the critical role of urgent surgical evacuation.

We report the case of a patient who underwent a vacuum-assisted biopsy of amorphous clustered microcalcifications complicated by a large compression-refractory hematoma secondary to pseudoaneurysm formation. Breast sonography was used to identify an actively bleeding vessel and guide compression. However, due to its unresponsiveness to conventional management and rapid progression, the hematoma required surgical evacuation and ligation of the bleeding vessel. This suggests that, in the face of significant intractable bleeding, a heightened awareness of the possible need for surgical intervention should be maintained.