Primary MALT lymphoma of the breast: pathological and radiological characteristics.

PURPOSE: Primary Mucosa-associated lymphoid tissue (MALT) lymphoma is a rare diagnosis in the breast, and clinical diagnosis based on radiological features is often challenging. This study aimed to evaluate the clinicopathological, and radiological characteristics of the patients diagnosed with primary breast MALT lymphoma. METHODS: This study examined 18 cases of primary MALT lymphoma of the breast diagnosed at a single tertiary center between January 2002 to December 2020. Medical charts, radiological imaging and original pathology slides were reviewed for each case. RESULTS: All cases were female (gender assigned at birth) and presented with a palpable mass or an incidental imaging finding. Imaging presentation ranged from mammographic asymmetries, circumscribed masses, and ultrasound masses lacking suspicious features. Seventeen cases were biopsied under ultrasound; one received a diagnostic excision biopsy. Microscopic examination of the breast specimens demonstrated atypical small lymphocyte infiltration with plasmacytoid differentiation and rare lymphoepithelial lesions. Immunohistochemistry was performed in all cases and established the diagnosis. Most patients were treated with radiotherapy, and only three were treated with chemotherapy. The median follow-up period was 4 years and 7.5 months, and all patients were alive at the last follow-up. CONCLUSION: Primary MALT breast lymphomas are usually indolent and non-systemic, and local radiotherapy may effectively alleviate local symptoms. Radiological findings show overlap with benign morphological features, which can delay the diagnosis of this unusual etiology. Although further studies involving a larger cohort could help establish the clinical and radiological characteristics of primary breast MALT lymphomas, pathology remains the primary method of diagnosis. TRIAL REGISTRATION NUMBER: University Health Network Ethics Committee (CAPCR/UHN REB number 19-5844), retrospectively registered.

[SCREENING WOMEN AT HIGH RISK FOR BREAST CANCER - BRCA AND BEYOND].

BACKGROUND: Radiologic screening for breast cancer is performed with the goal of diagnosing the disease at an earlier stage, thus reducing morbidity and mortality. Screening recommendations for women at higher than average risk for breast cancer differ from those of women with an average risk, and include yearly breast MRI and mammography starting at a young age. OBJECTIVES: Review the morbidity and mortality, and check whether the goal of early diagnosis was achieved in the participants of the High-Risk Ontario Breast Screening Program at the Princess Margaret Cancer Centre, Ontario Canada. METHODS: A prospective cohort study was conducted of 2,081 women participating in the Princess Margaret Cancer Centre high risk screening program 2011-2018. Demographic, imaging, and if applicable biopsies, diagnosis and treatment data were captured in a prospectively maintained database starting with each participant's enrolment in the program. RESULTS: A total of 32% of the participants were carriers of pathogenic variants in breast cancer related genes (BRCA, NF, CHEK2, TP53 etc.), 8% had a history of therapeutic chest radiotherapy, and the remaining 60% had a calculated elevated lifetime risk based on family history or personal risk factors, without an identifiable pathogenic mutation or previous radiation. During the follow-up period 89 breast cancer cases were diagnosed at the median age of 49 years. Median tumor size at diagnosis was 0.9 cm, correlating with a T1 disease. Nodal disease was found only in 4 cases. Breast cancer incidence was the same in the mutation carriers and chest radiotherapy groups, but 3-fold lower in the third group. Diagnosis of breast cancer was most commonly conducted by MRI imaging, and only 6% of cases were diagnosed based solely on mammography findings. Furthermore, 38 women died during follow-up, 29 of them (76%) were BRCA carriers who died from ovarian carcinoma. CONCLUSIONS: Diagnosis at an early stage was achieved in this cohort of women followed in the high risk screening program. Most cases were diagnosed by MRI, thus emphasizing the importance of identifying women at high risk for breast cancer and referring them to the appropriate screening program.

Longitudinal Study of Psychosocial Outcomes Following Surgery in Women with Unilateral Nonhereditary Breast Cancer.

INTRODUCTION: Rates of bilateral mastectomy are rising in women with unilateral, nonhereditary breast cancer. We aim to characterize how psychosocial outcomes evolve after breast cancer surgery. PATIENTS AND METHODS: We performed a prospective cohort study of women with unilateral, sporadic stage 0-III breast cancer at University Health Network in Toronto, Canada between 2014 and 2017. Women completed validated psychosocial questionnaires (BREAST-Q, Impact of Event Scale, Hospital Anxiety & Depression Scale) preoperatively, and at 6 and 12 months following surgery. Change in psychosocial scores was assessed between surgical groups using linear mixed models, controlling for age, stage, and adjuvant treatments. P < .05 were significant. RESULTS: A total of 475 women underwent unilateral lumpectomy (42.5%), unilateral mastectomy (38.3%), and bilateral mastectomy (19.2%). There was a significant interaction (P < .0001) between procedure and time for breast satisfaction, psychosocial and physical well-being. Women having unilateral lumpectomy had higher breast satisfaction and psychosocial well-being scores at 6 and 12 months after surgery compared with either unilateral or bilateral mastectomy, with no difference between the latter two groups. Physical well-being declined in all groups over time; scores were not better in women having bilateral mastectomy. While sexual well-being scores remained stable in the unilateral lumpectomy group, scores declined similarly in both unilateral and bilateral mastectomy groups over time. Cancer-related distress, anxiety, and depression scores declined significantly after surgery, regardless of surgical procedure (P < .001). CONCLUSIONS: Psychosocial outcomes are not improved with contralateral prophylactic mastectomy in women with unilateral breast cancer. Our data may inform women considering contralateral prophylactic mastectomy.

Surgical Morbidity of Full-Thickness Chest Wall Resection for Breast Cancer: A Retrospective Study of a National Database.

BACKGROUND: Full-thickness chest wall resection (FTCWR) is an underused modality for treating locally advanced primary or recurrent breast cancer invading the chest wall, for which little data exist regarding morbidity and mortality. We examined the postoperative complication rates in breast cancer patients undergoing FTCWR using a large multinational surgical outcomes database. METHODS: A retrospective cohort analysis was conducted using the American College of Surgeons National Surgical Quality Improvement Program database. All patients undergoing FTCWR for breast cancer between 2007 and 2016 were identified (n = 137). Primary outcome measures included 30-d postoperative morbidity, composite respiratory complications, and hospital length of stay (LOS). The secondary aim was to compare the postoperative morbidity of FTCWR to those of patients undergoing mastectomy. One-to-one coarsened exact matching was conducted between two groups, which were then compared with respect to morbidity, mortality, reoperations, readmissions, and LOS. RESULTS: The overall rate of postoperative morbidity was 11.7%. Two patients (1.5%) had respiratory complications requiring intubation. Median hospital LOS was 2 d. In the coarsened exact matching analysis, 122 patients were included in each of the two groups. Comparison of matched cohorts demonstrated an overall morbidity for the FTCWR group of 11.5% compared with 8.2% for the mastectomy group (8.2%) (P = 0.52). CONCLUSIONS: FTCWR for the local treatment of breast cancer can be performed with relatively low morbidity and respiratory complications. This is the largest study looking at postoperative complications for FTCWR in the treatment of breast cancer. Future studies are needed to determine the long-term outcomes of FTCWR in this patient population.

Does oncoplastic surgery increase immediate (30-day) postoperative complications? An analysis of the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database.

PURPOSE: Although there has been a significant increase in the use of oncoplastic surgery (OPS), data on the postoperative safety of this approach are limited compared to traditional lumpectomy. This study aimed to compare the immediate (30-day) postoperative complications associated with OPS and traditional lumpectomy. METHODS: An analysis of the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database was performed on women with breast cancer who underwent OPS or traditional lumpectomy. Logistic regression was used to explore the effect of type of surgery on the outcome of interest. RESULTS: A total of 109,487 women were analyzed of whom 8.3% underwent OPS. OPS had a longer median operative time than traditional lumpectomy. The unadjusted immediate (30-day) overall complication rate was significantly higher with OPS than traditional lumpectomy (3.8% versus 2.6%, p < 0.001). After adjusting for baseline differences, overall 30-day postoperative complications were significantly higher amongst women undergoing OPS compared with traditional lumpectomy (OR 1.41, 95%CI 1.24-1.59). Factors that were independent predictors of overall 30-day complications included higher age, higher BMI, race, smoking status, lymph node surgery, neoadjuvant chemotherapy, ASA class ≥ 3, in situ disease, and year of operation. The interaction term between type of surgery and operative time was not statistically significant, indicating that operative time did not modify the effect of type of surgery on immediate postoperative complications. CONCLUSIONS: Although there were slightly higher overall complication rates with OPS, the absolute rates remained quite low for both groups. Therefore, OPS may be performed in women with breast cancer who are suitable candidates.

Screening women at high risk for breast cancer: one program fits all? : Subgroup analysis of a large population high risk breast screening program.

INTRODUCTION: The Ontario High Risk Breast Screening program follows women aged 30-69 at an increased risk of breast cancer, using a yearly mammography and breast MRI. The aim of this study is to determine the clinical outcomes for the enrolled women. METHODS: Observational cohort study following 2081 participants in the high-risk screening program 2011-2017. The participants were divided into three subgroup according to their risk criteria: (a) known carriers of pathogenic variants (PV) in hereditary breast cancer genes. (b) Previous chest radiotherapy. (c) Estimated life time risk (ELR) ≥ 25%, calculated using the International Breast Cancer Intervention Study (IBIS) tool, with no known mutation or previous radiation. All Breast Cancer (BC) diagnosed during the follow-up time were recorded. RESULTS: 673 women carried PVs in hereditary breast cancer genes, 159 had a history of chest radiotherapy, and 1249 had an ELR ≥ 25%. The total cohort of screening years was 8126. Median age at BC diagnosis was 41 for the first group, 47 for the second group and 51 for the third. BC incidence rate was 18.2 for PV mutation carriers, 17.9 for the chest radiotherapy group and 6.2 for ELR ≥ 25%. Hazard ratio was similar for the first two groups, but significantly lower for the ELR ≥ 25% group. When stratifying by age, the incidence rate in the ELR ≥ 25% increased over time, until it became similar to that of the other subgroups after age 50. CONCLUSION: Our findings question the need to screen women with an elevated lifetime risk using the same screening practices used for women who are PV mutation carriers, or with a history of chest radiation, prior to the age of 50.

Predictors of uptake of contralateral prophylactic mastectomy in women with nonhereditary breast cancer.

BACKGROUND: The rates of contralateral prophylactic mastectomy (CPM) are increasing in women with breast cancer. Previous retrospective research has examined clinical and demographic predictors of the uptake of CPM. However, to the authors' knowledge, there has been very little prospective research to date that has examined psychosocial functioning prior to breast cancer surgery to determine whether psychosocial functioning predicts uptake of CPM. The current study was conducted to evaluate demographic, clinical, and psychosocial predictors of the uptake of CPM in women with unilateral breast cancer without a BRCA1 or BRCA2 mutation. METHODS: Women with unilateral non-BRCA-associated breast cancer completed questionnaires prior to undergoing breast cancer surgery. Participants completed demographic and psychosocial questionnaires assessing anxiety, depression, cancer-related distress, optimism/pessimism, breast satisfaction, and quality of life. Pathological and surgical data were collected from medical charts. RESULTS: A total of 506 women consented to participate, 112 of whom (22.1%) elected to undergo CPM. Age was found to be a significant predictor of CPM, with younger women found to be significantly more likely to undergo CPM compared with older women (P < .0001). The rate of CPM was significantly higher in women with noninvasive breast cancer compared with those with invasive breast cancer (P < .0001). Women who elected to undergo CPM had lower levels of presurgical breast satisfaction (P = .01) and optimism (P = .05) compared with women who did not undergo CPM. CONCLUSIONS: Psychosocial functioning at the time of breast cancer surgery decision making impacts decisions related to CPM. Women who have lower levels of breast satisfaction (body image) and optimism are more likely to elect to undergo CPM. It is important for health care providers to take psychosocial functioning into consideration when discussing surgical options.

Is immediate breast reconstruction safe in women over 70? An analysis of the National Surgical Quality Improvement Program (NSQIP) database.

PURPOSE: The safety of immediate breast reconstruction (IBR) in older women is largely unknown. This study aimed to determine the 30-day postoperative complication rates following IBR (implant-based or autologous) in older women (≥ 70 years) with breast cancer and to compare them to younger women (18-69 years). METHODS: The National Surgical Quality Improvement Program (NSQIP) database was used to identify women with in situ or invasive breast cancer who underwent IBR (2005-2016). Outcomes included 30-day postoperative morbidity and mortality, which were compared across age groups stratified by type of reconstruction. RESULTS: Of 28,850 women who underwent implant-based and 9123 who underwent autologous reconstruction, older women comprised 6.5% and 5.7% of the sample, respectively. Compared to younger women, older women had more comorbidities, shorter operative times, and longer length of hospital stay. In the implant-based reconstruction group, the 30-day morbidity rate was significantly higher in older women (7.5% vs 5.3%, p < 0.0001) due to higher rates of infectious, pulmonary, and venous thromboembolic events. Wound morbidity and prosthesis failure occurred equally among age groups. In the autologous reconstruction group, there was no statistically significant difference in the 30-day morbidity rates (older 9.5% vs younger 11.6%, p = 0.15). Both wound morbidity and flap failure rates were similar between the two age groups. For both reconstruction techniques, mortality within 30 days of breast surgery was rare. CONCLUSION: Immediate breast reconstruction is safe in older women. These data support the notion that surgeons should discuss IBR as a safe and integral part of cancer treatment in well-selected older women.

Psychosocial Functioning in Women with Early Breast Cancer Treated with Breast Surgery With or Without Immediate Breast Reconstruction.

PURPOSE: To compare psychosocial function outcomes in early breast cancer patients treated with breast-conserving surgery (BCS), mastectomy alone (MA), and mastectomy with immediate breast reconstruction (IBR) at 1 year after surgery. METHODS: Early-stage (stage 0-2) breast cancer patients treated with BCS, MA, and IBR at the University Health Network, Toronto, Ontario, Canada between May 1 2015 and July 31 2016 were prospectively enrolled. Their changes in psychosocial functioning from baseline to 12 months following surgery were compared by using the BREAST-Q, Hospital Anxiety and Depression Scale, and Impact of Event Scale with ANOVA and linear regression. RESULTS: There were 303 early-stage breast cancer patients: 155 underwent BCS, 78 MA, and 70 IBR. After multivariable regression accounting for age, baseline score, income, education, receipt of chemoradiation or hormonal therapy, ethnicity, cancer stage, and unilateral versus bilateral surgery, breast satisfaction was highest in BCS (72.1, SD 19.6), followed by IBR (60.0, SD 18.0), and MA (49.9, SD 78.0) at 12 months, p < 0.001. Immediate breast reconstruction had similar psychosocial well-being (69.9, SD 20.6) compared with BCS (78.5, SD 20.6), p = 0.07. Sexual and chest physical well-being were similar between IBR, BCS, and MA, p > 0.05. CONCLUSIONS: Our study found that in a multidisciplinary breast cancer centre where all three breast ablative and reconstruction options are available to early breast cancer patients, either BCS or IBR can be used to provide patients with a higher degree of satisfaction and psychosocial well-being compared with MA in the long-term.

Regional Nodal Irradiation in Early-Stage Breast Cancer.

BACKGROUND: Most women with breast cancer who undergo breast-conserving surgery receive whole-breast irradiation. We examined whether the addition of regional nodal irradiation to whole-breast irradiation improved outcomes. METHODS: We randomly assigned women with node-positive or high-risk node-negative breast cancer who were treated with breast-conserving surgery and adjuvant systemic therapy to undergo either whole-breast irradiation plus regional nodal irradiation (including internal mammary, supraclavicular, and axillary lymph nodes) (nodal-irradiation group) or whole-breast irradiation alone (control group). The primary outcome was overall survival. Secondary outcomes were disease-free survival, isolated locoregional disease-free survival, and distant disease-free survival. RESULTS: Between March 2000 and February 2007, a total of 1832 women were assigned to the nodal-irradiation group or the control group (916 women in each group). The median follow-up was 9.5 years. At the 10-year follow-up, there was no significant between-group difference in survival, with a rate of 82.8% in the nodal-irradiation group and 81.8% in the control group (hazard ratio, 0.91; 95% confidence interval [CI], 0.72 to 1.13; P=0.38). The rates of disease-free survival were 82.0% in the nodal-irradiation group and 77.0% in the control group (hazard ratio, 0.76; 95% CI, 0.61 to 0.94; P=0.01). Patients in the nodal-irradiation group had higher rates of grade 2 or greater acute pneumonitis (1.2% vs. 0.2%, P=0.01) and lymphedema (8.4% vs. 4.5%, P=0.001). CONCLUSIONS: Among women with node-positive or high-risk node-negative breast cancer, the addition of regional nodal irradiation to whole-breast irradiation did not improve overall survival but reduced the rate of breast-cancer recurrence. (Funded by the Canadian Cancer Society Research Institute and others; MA.20 ClinicalTrials.gov number, NCT00005957.).

Concurrent risk-reduction surgery in patients with increased lifetime risk for breast and ovarian cancer: an analysis of the National Surgical Quality Improvement Program (NSQIP) database.

BACKGROUND: Patients with genetic susceptibility to breast and ovarian cancer are eligible for risk-reduction surgery. Surgical morbidity of risk-reduction mastectomy (RRM) with concurrent bilateral salpingo-oophorectomy (BSO) is unknown. Outcomes in these patients were compared to patients undergoing RRM without BSO using a large multi-institutional database. METHODS: A retrospective cohort analysis was conducted using the American College of Surgeon's National Surgical Quality Improvement Program (NSQIP) 2007-2016 datasets, comparing postoperative morbidity between patients undergoing RRM with patients undergoing RRM with concurrent BSO. Patients with genetic susceptibility to breast/ovarian cancer undergoing risk-reduction surgery were identified. The primary outcome was 30-day postoperative major morbidity. Secondary outcomes included surgical site infections, reoperations, readmissions, length of stay, and venous thromboembolic events. A multivariate analysis was performed to determine predictors of postoperative morbidity and the adjusted effect of concurrent BSO on morbidity. RESULTS: Of the 5470 patients undergoing RRM, 149 (2.7%) underwent concurrent BSO. The overall rate of major morbidity and postoperative infections was 4.5% and 4.6%, respectively. There was no significant difference in the rate of postoperative major morbidity (4.5% vs 4.7%, p = 0.91) or any of the secondary outcomes between patients undergoing RRM without BSO vs. those undergoing RRM with concurrent BSO. Multivariable analysis showed Body Mass Index (OR 1.05; p < 0.001) and smoking (OR 1.78; p = 0.003) to be the only predictors associated with major morbidity. Neither immediate breast reconstruction (OR 1.02; p = 0.93) nor concurrent BSO (OR 0.94; p = 0.89) were associated with increased postoperative major morbidity. CONCLUSION: This study demonstrated that RRM with concurrent BSO was not associated with significant additional morbidity when compared to RRM without BSO. Therefore, this joint approach may be considered for select patients at risk for both breast and ovarian cancer.

Evolving surgical treatment decisions for male breast cancer: an analysis of the National Surgical Quality Improvement Program (NSQIP) database.

BACKGROUND: Male breast cancer (MBC) is a rare malignancy, and gender-specific treatment outcomes are currently lacking. The use of a large, multi-national surgical-outcomes database may provide a better understanding of treatment patterns and postoperative morbidity in men who undergo oncological breast surgery. METHODS: A retrospective cohort analysis was conducted between 2007 and 2016 using the American College of Surgeons National Surgical Quality Improvement Program database (NSQIP), examining MBC treatment patterns and postoperative complication rates. All men undergoing surgery for the treatment of invasive or in situ carcinoma of the breast were identified. Clinical characteristics, demographics, and surgical treatment options most frequently used for this population were described. In addition, the 30-day postoperative complication rates in the surgical treatment of male breast cancer were evaluated. RESULTS: A total of 1773 MBC patients with a median age of 65 years (IQR 56-74 years) were included in this analysis. Mean body mass index (BMI) was 29.1 (IQR 25.4-33.8). In this study population, 177 (10.0%) had a diagnosis of in situ breast cancer, while the remaining 1596 (90.0%) had invasive disease. While most men underwent mastectomy, 282 (15.9%) had breast-conserving surgery. There were 74 (4.2%) patients who underwent immediate breast reconstruction. In addition, 118 (6.7%) patients elected to have a contralateral prophylactic mastectomy. Overall, the rate of morbidity was 4.6%, comprising mostly of wound complications (3.2%). CONCLUSION: Analysis of this large, prospective multi-institutional cohort revealed that complication rates are low and comparable to reported rates in the female breast cancer population. What is also significant about this analysis is that the cohort demonstrated the importance of cosmetic considerations in MBC patients, as some men decide to undergo breast-conserving surgery or immediate breast reconstruction. Contralateral prophylactic mastectomy in the treatment of MBC is also performed.

Society of Surgical Oncology Breast Disease Working Group Statement on Prophylactic (Risk-Reducing) Mastectomy.

Over the past several years, there has been an increasing rate of bilateral prophylactic mastectomy (BPM) and contralateral prophylactic mastectomy (CPM) surgeries. Since publication of the 2007 SSO position statement on the use of risk-reducing mastectomy, there have been significant advances in the understanding of breast cancer biology and treatment. The purpose of this manuscript is to review the current literature as a resource to facilitate a shared and informed decision-making process regarding the use of risk-reducing mastectomy.

Preoperative MRI of the breast and ipsilateral breast tumor recurrence: Long-term follow up.

BACKGROUND: Local recurrence after breast conserving surgery is reported in 5-10% of cases. This study aims to determine if preoperative MRI is associated with reduced IBTR rates in the longer term and evaluate IBTR rates of a high risk (TN and Her-2 positive) subgroup in those receiving MRI or not. METHODS: Between 1999 and 2005, patients with invasive breast cancer undergoing BCS and radiation were identified. Primary endpoint was IBTR rate. RESULTS: The cohort consisted of 470 cases: 27% underwent MRI and 73% did not. Median follow-up was 97 months. Overall 10-year IBTR rate was 3.6%. There was no significant difference in IBTR rate at 10 years between those receiving MRI or not (1.6% vs. 4.2% (P = 0.37). The TN and Her-2 positive combined subgroup had a higher IBTR rate than all others (9.8% vs. 1.7%, P = 0.001). In the group without MRI, the IBTR rate of the high risk group was 11.8% compared to 1.8% in the remainder (P = 0.002). CONCLUSION: With 10-year follow-up, there was no significant difference in IBTR rate whether preoperative MRI is performed versus not. The high risk population showed an increased IBTR rate, this was more marked in those who did not receive MRI.

The effect of surgery type on survival and recurrence in very young women with breast cancer.

BACKGROUND: The impact of surgical treatment on outcomes in breast cacner in very young women remains unclear. We sought to determine the effect of surgery type on risk of recurrence and survival in a population-based cohort. METHODS: All women diagnosed with breast cancer aged ≤35 (1994-2003) were identified from the Ontario Cancer Registry. Patient, tumor, and treatment variables, including primary surgery, recurrences, and death were abstracted from chart review. Cox regression models were fit to determine the effect of surgery type on recurrence and overall survival. RESULTS: We identified 1,381 patients with 11-year median follow-up of which 793 (57%) had BCS. Of the remaining mastectomy patients, 52% had postmastectomy radiation. Overall, 41% of patients sustained a recurrence of any type and 31% died. Controlling for known confounders, there was no association between type of surgery and death from any cause (HR = 0.98, 95% CI = 0.78, 1.25) or first recurrence (HR = 0.93, 95% CI = 0.75, 1.14). Distant recurrence was most common (13% in BCS; 25.3% in mastectomy) with local recurrence 12.4% after BCS and 7.5% after mastectomy. CONCLUSIONS: In this cohort of very young women who were selected for treatment with BCS and mastectomy, we found similar oncologic outcomes. J. Surg. Oncol. 2017;115:122-130. © 2017 Wiley Periodicals, Inc.

Post-mastectomy Radiation: Should Subtype Factor into the Decision?

BACKGROUND: Traditional indications do not factor molecular subtype into the decision making for post-mastectomy radiation (PMRT). We sought to determine whether constructed subtype was associated with receipt of PMRT in an academic cancer center and to assess differences in locoregional recurrence (LRR) by constructed subtype. METHODS: Patients treated with mastectomy as the primary surgical therapy were identified. Univariate and stepwise multivariate logistic regression analyses examined the association between covariates and PMRT. Kaplan-Meier estimates for the time to either the earlier of LRR or last follow-up were obtained for each subtype, and Cox proportional hazards regression examined the effect of covariates on time to LRR in both univariate analyses and stepwise multivariate analysis. RESULTS: Overall, 884 patients with invasive breast cancer who underwent a primary mastectomy between January 2002 and May 2012 were included in the study. A total of 359 patients (41.6 %) received PMRT. Compared with other subtypes, triple negative (TN; HR-/HER2-) cancers were more likely to be smaller (95 % T1/T2; p = 0.02) and have a lower nodal burden (N0 65 %; p < 0.0001). On multivariate analysis, age < 50 years, lymphovascular invasion (LVI), T stage, N stage, and close or positive margins remained significantly associated with PMRT, while constructed subtype was not associated with PMRT. Compared with all other subtypes, TN had the highest rate of LRR [hazard ratio (HR) 5.70; p < 0.0001]. On multivariable analysis, TN status, LVI, and not receiving chemotherapy were significantly associated with LRR. CONCLUSIONS: Despite significant differences in LRR by constructed subtype, receptor status does not appear to be associated with the receipt of PMRT. In our series, TN cancers had the highest risk of LRR despite their relatively smaller size and limited nodal disease.

TARGIT-R (Retrospective): North American Experience with Intraoperative Radiation Using Low-Kilovoltage X-Rays for Breast Cancer.

BACKGROUND: Single-dose intraoperative radiotherapy (IORT) is an emerging treatment for women with early stage breast cancer. The objective of this study was to define the frequency of IORT use, patient selection, and outcomes of patients treated in North America. METHODS: A multi-institutional retrospective registry was created, and 19 institutions using low-kilovoltage IORT for the treatment of breast cancer entered data on patients treated at their institution before July 31, 2013. Patient selection, IORT treatment details, complications, and recurrences were analyzed. RESULTS: From 2007 to July 31, 2013, a total of 935 women were identified and treated with lumpectomy and IORT. A total of 822 patients had at least 6 months' follow-up documented and were included in the analysis. The number of IORT cases performed increased significantly over time (p < 0.001). The median patient age was 66.8 years. Most patients had disease that was <2 cm in size (90 %) and was estrogen positive (91 %); most patients had invasive ductal cancer (68 %). Of those who had a sentinel lymph node procedure performed, 89 % had negative sentinel lymph nodes. The types of IORT performed were primary IORT in 79 %, secondary IORT in 7 %, or planned boost in 14 %. Complications were low. At a median follow-up of 23.3 months, crude in-breast recurrence was 2.3 % for all patients treated. CONCLUSIONS: IORT use for the treatment of breast cancer is significantly increasing in North America, and physicians are selecting low-risk patients for this treatment option. Low complication and local recurrence rates support IORT as a treatment option for selected women with early stage breast cancer.

Changes in insulin receptor signaling underlie neoadjuvant metformin administration in breast cancer: a prospective window of opportunity neoadjuvant study.

INTRODUCTION: The antidiabetic drug metformin exhibits potential anticancer properties that are believed to involve both direct (insulin-independent) and indirect (insulin-dependent) actions. Direct effects are linked to activation of AMP-activated protein kinase (AMPK) and an inhibition of mammalian target of rapamycin mTOR signaling, and indirect effects are mediated by reductions in circulating insulin, leading to reduced insulin receptor (IR)-mediated signaling. However, the in vivo impact of metformin on cancer cell signaling and the factors governing sensitivity in patients remain unknown. METHODS: We conducted a neoadjuvant, single-arm, "window of opportunity" trial to examine the clinical and biological effects of metformin on patients with breast cancer. Women with untreated breast cancer who did not have diabetes were given 500 mg of metformin three times daily for ≥2 weeks after diagnostic biopsy until surgery. Fasting blood and tumor samples were collected at diagnosis and surgery. Blood glucose and insulin were assayed to assess the physiologic effects of metformin, and immunohistochemical analysis of tumors was used to characterize cellular markers before and after treatment. RESULTS: Levels of IR expression decreased significantly in tumors (P = 0.04), as did the phosphorylation status of protein kinase B (PKB)/Akt (S473), extracellular signal-regulated kinase 1/2 (ERK1/2, T202/Y204), AMPK (T172) and acetyl coenzyme A carboxylase (S79) (P = 0.0001, P < 0.0001, P < 0.005 and P = 0.02, respectively). All tumors expressed organic cation transporter 1, with 90% (35 of 39) exhibiting an Allred score of 5 or higher. CONCLUSIONS: Reduced PKB/Akt and ERK1/2 phosphorylation, coupled with decreased insulin and IR levels, suggest insulin-dependent effects are important in the clinical setting. These results are consistent with beneficial anticancer effects of metformin and highlight key factors involved in sensitivity, which could be used to identify patients with breast cancer who may be responsive to metformin-based therapies. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00897884. Registered 8 May 2009.

'Taking control of cancer': understanding women's choice for mastectomy.

PURPOSE: Rates of both unilateral (UM) and contralateral prophylactic mastectomy (CPM) for unilateral early-stage breast cancer (ESBC) have been increasing since 2003. Recent studies suggest that this increase may be due to women choosing UM and CPM because of fear. We conducted an in-depth qualitative study to identify those factors influencing a woman's choice for more extensive surgery. METHODS: Semi-structured interviews were conducted with breast cancer patients to examine the experiences, decision making, and choice of UM ± CPM for the treatment of ESBC. Purposive sampling identified suitable candidates for breast-conserving therapy (BCT) who underwent UM ± CPM. Interviews were guided by grounded theory methodology, and constant comparative analysis identified key concepts and themes. RESULTS: Data saturation was achieved after 29 interviews. 'Taking control of cancer' was the dominant theme. Fear of breast cancer was expressed at diagnosis and remained throughout decision making. Personal experiences of family or friends 'living with cancer' were the most influential source of information during the decision-making process. Fear translated into an overestimated risk of recurrence, contralateral breast cancer (CBC), and death. Despite surgeons discussing equivalent survival with BCT, UM ± CPM patients believed that by choosing UM ± CPM they would eliminate recurrence, CBC and live longer. By choosing more extensive surgery, women were actively trying to control cancer outcomes as more surgery was believed to offer greater survival. CONCLUSIONS: Women seek UM and CPM to take control of cancer and manage their fear. It is important for surgeons to understand how personal experiences shape women's choice for UM ± CPM to facilitate informed decision making.

The Importance of Applying ACOSOG Z0011 Criteria in the Axillary Management of Invasive Lobular Carcinoma: A Multi-institutional Cohort Study.

BACKGROUND: The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial led to a significant change in the management of patients with early stage breast cancer and limited sentinel lymph node (SLN) metastases. However, only 27 patients with invasive lobular carcinoma (ILC) were randomized to the completion axillary lymph node dissection (ALND) arm. To assess the generalizability of the Z0011 trial, the primary aim of this study was to determine the risk of residual nodal burden (RNB) for ILC. METHODS: A multi-institutional cohort study was completed. RNB was determined for women of any age with an ILC and at least one positive SLN who underwent a primary breast procedure (lumpectomy or mastectomy) and both a SLN biopsy followed by a completion ALND between July 1, 1999, and June 30, 2009, at two large academic centers. RESULTS: A total of 59 patients (60 ILCs) met the inclusion criteria. Although the overall RNB was 40%, it was significantly greater in the T3+ group compared to T1/T2 (87 vs. 24%, respectively, p < 0.0001). When comparing only ILCs that met all of the inclusion criteria for ACOSOG Z0011 (T1 or T2, 1 or 2 SLNs positive, no SLN extranodal extension, and breast conservation) to those ILCs that did not, the RNB was significantly greater in the latter (56 vs. 17 %; p < 0.003). CONCLUSIONS: Overall, the clinical practice changes that have occurred after publication of the ACOSOG Z0011 trial appear to be generalizable to ILCs within the inclusion criteria of the study.