Germline Genetic Testing Among Women ≤ 45 Years of Age with Ductal Carcinoma In Situ Versus Invasive Breast Cancer in a Large Integrated Health Care System.

BACKGROUND: We compared the results of hereditary cancer multigene panel testing among patients ≤ 45 years of age diagnosed with ductal carcinoma in situ (DCIS) versus invasive breast cancer (IBC) in a large integrated health care system. METHODS: A retrospective cohort study of hereditary cancer gene testing among women ≤ 45 years of age diagnosed with DCIS or IBC at Kaiser Permanente Northern California between September 2019 and August 2020 was performed. During the study period, institutional guidelines recommended the above population be referred to genetic counselors for pretesting counseling and testing. RESULTS: A total of 61 DCIS and 485 IBC patients were identified. Genetic counselors met with 95% of both groups, and 86.4% of DCIS patients and 93.9% of IBC patients (p = 0.0339) underwent gene testing. Testing differed by race/ethnicity (p = 0.0372). Among those tested, 11.76% (n = 6) of DCIS patients and 16.71% (n = 72) of IBC patients had a pathogenic variant (PV) or likely pathogenic variant (LPV) based on the 36-gene panel (p = 0.3650). Similar trends were seen in 13 breast cancer (BC)-related genes (p = 0.0553). Family history of cancer was significantly associated with both BC-related and non-BC-related PVs in IBC, but not DCIS. CONCLUSION: In our study, 95% of patients were seen by a genetic counselor when age was used as an eligibility criterion for referral. While larger studies are needed to further compare the prevalence of PVs/LPVs among DCIS and IBC patients, our data suggest that even in younger patients, the prevalence of PVs/LPVs in BC-related genes is lower in DCIS patients.

Outcomes of DCIS treated with breast conserving surgery without radiotherapy on recurrence, survival, and health-related quality of life.

BACKGROUND: Sector resection for Ductal Carcinoma in Situ (DCIS) allows wide excision without compromising breast shape. There are concerns that radiotherapy for some DCIS after sector resection is unnecessary and reduces patient satisfaction and quality of life without affecting survival. This study aimed to investigate whether women with DCIS managed with sector resection without radiotherapy had acceptable rates of recurrence and health-related quality of life outcomes. METHODS: Retrospective study of patients who underwent sector resection for DCIS without adjuvant radiotherapy from 1992 to 2021. Tumour size, grade, necrosis, margins, follow up and time to ipsilateral recurrence was recorded. Patients were posted a BREAST-Q to assess health-related quality of life. RESULTS: One hundred and thirty-eight patients were treated for pure DCIS by two surgeons from 1992 to 2018. One hundred and sixteen patients underwent sector resection, 22 had mastectomy. Average age 61 years. Mean follow up 9.14 years. Recurrence rate after sector resection was 18.97%. 55% were DCIS. Annualized recurrence rate was 2.07%. There were no cancer-related deaths. BREAST-Q completion rate was 44%. Satisfaction with breasts, physical, psychosocial, and sexual well-being scores were significantly higher than normative Australian values and a mixed cohort of women who underwent breast conserving surgery with radiotherapy. CONCLUSION: DCIS can be safely managed with sector resection without radiotherapy and regular long-term follow up. This approach results in low annualized recurrence rates, high levels patient satisfaction and health-related quality of life and should be considered a safe alternative for patients with DCIS to minimize morbidity without affecting cancer survival.

Factors associated with ductal carcinoma in situ (DCIS) treatment patterns and patient-reported outcomes across a large integrated health network.

PURPOSE: To examine associations between ductal carcinoma in situ (DCIS) patients' characteristics, treating locations and DCIS treatments received and to pilot assessing quality-of-life (QoL) values among DCIS patients with diverse backgrounds. METHODS: We performed a retrospective tumor registry review of all patients diagnosed and treated with DCIS from 2018 to 2019 in the UPMC-integrated network throughout central and western Pennsylvania. Demographics, clinical information, and administered treatments were compiled from tumor registry records. We categorized contextual factors such as different hospital setting (academic vs. community), socioeconomic status based on the neighborhood deprivation index (NDI) as well as age and race. QoL survey was administered to DCIS patients with diverse backgrounds via QoL questionnaire breast cancer module 23 and qualitative assessment questions. RESULTS: A total of 912 patients were reviewed. There were no treatment differences noted for age, race, or NDI. Mastectomy rate was higher in academic sites than community sites (29 vs. 20.4%; p = 0.0045), while hormone therapy (HT) utilization rate was higher in community sites (74 vs. 62%; p = 0.0012). QoL survey response rate was 32%. Only HT side effects negatively affected in QoL scores and there was no significant difference in QoL domains and decision-making process between races, age, NDI, treatment groups, and treatment locations. CONCLUSION: Our integrated health network did not show chronically noted disparities arising from social determinates of health for DCIS treatments by implementing clinical pathways and system-wide peer review. Also, we demonstrated feasibility in collecting QoL for DCIS women with diverse backgrounds and different socioeconomic statuses.

Changes in Serum Trace Element Concentrations Before and After Surgery in Resectable Breast Cancer.

BACKGROUND/AIM: Minerals and trace elements (TEs) play vital roles in normal biological functions and in all cancers. Breast carcinoma is the most commonly occurring cancer in women. The aim of this study was to evaluate changes in TE levels before and after breast cancer surgery and the clinical utility and reliability of TE levels assayed using inductively coupled plasma mass spectrometry (ICP-MS). PATIENTS AND METHODS: Thirteen patients with ductal carcinoma in situ (DCIS) and 34 with invasive ductal carcinoma (IDC) treated with planned surgery were enrolled between August 2017 and February 2019. Blood samples were collected before and the day after resection of the primary tumor. All enrolled patients received mastectomy or quadrantectomy and axillary lymph node dissection/biopsy. Serum TE concentrations were determined using ICP-MS. RESULTS: Changes in boron, titanium, vanadium, chromium, copper, zinc, and selenium levels from before to after surgery differed between IDC and DCIS patients. Boron and copper levels before surgery and changes in titanium, vanadium, and chromium before and after surgery are potential predictors distinguishing DCIS from IDC. Subset analysis showed that chromium is a potential biomarker for luminal subtype, while titanium and chromium are potential biomarkers for pathological staging. CONCLUSION: Changes in serum TEs before and after surgery may help with diagnosis and staging of breast cancer and in establishing TE supplementation protocols.

Economic Impact of Reducing Reexcision Rates after Breast-Conserving Surgery in a Large, Integrated Health System.

BACKGROUND: Reexcision after breast-conserving surgery (BCS) is costly for patients, but few studies have captured the economic burden to a healthcare system. We quantified operating room (OR) charges as well as OR time and then modeled expected savings of a reexcision reduction initiative. METHODS: We performed a retrospective cohort review of all breast cancer patients with BCS between January 1, 2016 and December 31, 2020. Operating room charges of disposable supplies and implants as well as operative time were calculated. RESULTS: During the 5-year period, the 8804 patients who underwent BCS, 1628 (18.5%) required reexcision. The reexcision cohort was younger (61 vs. 64 years, p < 0.001), more likely to have ductal carcinoma in situ (DCIS) (23.7% vs. 15.2%, p < 0.001), and had larger tumors (T1+T2 73.2% vs. 83.1%, p < 0.001). Reexcision costs represented 39% of total costs, the cost per patient for surgery was fourfold higher for reexcision patients. Reexcision operations comprised 14% of total operating room (OR) time (1848 of 13,030 hours). The reexcision rate for 54 surgeons varied from 7.2-39.0% with 46% (n = 25) having a reexcision rate >20%. A model simulating reducing reexcision rates to 20% or below for all surgeons reduced the reexcision rate to 16.2% overall. Using per procedure data, the model predicted a decrease in reexcision operations by 18% (327 operations), OR costs by 14% ($287,534), and OR time by 11% (204 hours). CONCLUSIONS: Reexcision after BCS represents 39% of direct OR costs and 14% of OR time in our healthcare system. Modest improvements in surgeon reexcision rates may lead to significant economic and OR time savings.

Phylogenetic analysis of combined lobular and ductal carcinoma of the breast.

Breast cancer manifests in diverse forms, with particular reference to various cell types harboring different mutations and gene expression profiles. To elucidate the clonal relationship between cancer cells in tumors composed of both ductal and lobular phenotypes, two combined lobular and ductal carcinoma (CLDC) cases were analyzed, including one mixed ductal­lobular carcinoma (MDL) lesion, by direct sequencing of the mitochondrial DNA D­loop, digital PCR targeting of chromosomes 1q and 16q, as well as next­generation sequencing. DNA was extracted from formalin­fixed paraffin­embedded tissue sections of different histological types, including invasive ductal carcinoma, invasive lobular carcinoma, ductal carcinoma in situ, lobular carcinoma in situ, flat epithelial atypia, non­neoplastic mammary gland and extramammary organs, using laser­assisted microdissection. Mutations detected by the comprehensive cancer panel were validated by SYBR green allele­specific quantitative PCR (RRM1, AKT1, PIK3CA, RALGDS, EGFR, TP53, IL21R, DPYD, SGK1, CDH1, TIMP3 and KMT2C). CLDC, which shared the basic genetic alterations of 1q gain or 16q loss, progresses to invasive lobular or ductual carcinoma with the accumulation of further mutations. Cancer cells contained in an MDL lesion shared closely related genetic alterations, suggesting that these cells have the same origin, despite different histological features, namely 'lobular' or 'ductal'. By contrast, multiple lesions located away from the main tumor, diagnosed as CLDC (excluding an MDL lesion) were not always identical with different genetic alterations, despite being diagnosed as ductal carcinoma in situ. Thus, MDL should be defined as a distinct category separate from CLDC, whose components of 'lobular' and 'ductal' may have the same cellular origin.

Management of High-Risk Breast Lesions.

High-risk breast lesions (HRLs) are a group of heterogeneous lesions that can be associated with a synchronous or adjacent breast cancer and that confer an elevated lifetime risk of breast cancer. Management of HRLs after core needle biopsy may include close imaging and clinical follow-up or excisional biopsy to evaluate for cancer. This article reviews histologic features and clinical presentation of each of the HRLs, current evidence with regard to management, and guidelines from the American Society of Breast Surgeons and National Comprehensive Cancer Network. In addition, imaging surveillance and risk-reduction strategies for women with HRLs are discussed.

Impact of Cribriform Pattern and Intraductal Carcinoma on Gleason 7 Prostate Cancer Treated with External Beam Radiotherapy.

PURPOSE: We assessed the impact of cribriform pattern and/or intraductal carcinoma on Gleason 7 prostate cancer treated with external beam radiotherapy. METHODS: We evaluated men with Gleason 7 (Grade Groups 2 and 3) prostate cancer treated with dose escalated external beam radiotherapy with or without androgen deprivation. We reviewed biopsies for the presence of cribriform pattern and/or intraductal carcinoma. Study end points included biochemical recurrence-free, distant metastasis-free and disease specific survival. RESULTS: In the 237 patients median followup was 117 months (range 3 to 236). According to National Comprehensive Cancer Network® risk groups 24% of patients were at favorable intermediate risk, 53% were at unfavorable intermediate risk and 23% were at high risk. The rate of cribriform pattern without intraductal carcinoma, cribriform pattern with intraductal carcinoma, intraductal carcinoma without cribriform pattern and none of these morphologies was 36%, 13%, 0% and 51%, respectively. On multivariable analysis cribriform pattern with intraductal carcinoma (HR 4.22, 95% CI 2.08-8.53, p <0.0001), prostate specific antigen 10 to 20 ng/ml (HR 1.97, 95% CI 1.03-3.79, p=0.04) and prostate specific antigen greater than 20 ng/ml (HR 2.26, 95% CI 1.21-4.23, p=0.01) were associated with worse biochemical recurrence-free survival. On multivariable analysis only cribriform pattern with intraductal carcinoma was associated with inferior distant metastasis-free survival (HR 4.18, 95% CI 1.43-12.28, p=0.01) and disease specific survival (HR 14.26, 95% CI 2.75-74.04, p=0.0016). Factors associated with cribriform pattern with or without intraductal carcinoma included Grade Group 3, high risk group and 50% or more positive biopsy cores. When stratified by neither morphology present, cribriform pattern without intraductal carcinoma and cribriform pattern with intraductal carcinoma the differences in biochemical recurrence-free, distant metastasis-free and disease specific survival were statistically significant (p=0.00042, p=0.017 and p <0.0001, respectively). CONCLUSIONS: Cribriform pattern with intraductal carcinoma was associated with adverse outcomes in men with Gleason 7 prostate cancer treated with external beam radiotherapy while cribriform pattern without intraductal carcinoma was not so associated. Future studies may benefit from dichotomizing these 2 histological entities.

Hyperthermic chest wall re-irradiation in recurrent breast cancer: a prospective observational study.

PURPOSE: To prospectively investigate the role of re-irradiation (re-RT) combined with hyperthermia (HT) in a contemporary cohort of patients affected by recurrent breast cancer (RBC). METHODS: Within the prospective registry HT03, patients with resected RBC and previous irradiation were included. Re-RT was applied to the recurrence region with doses of 50-50.4 Gy, with a boost up to 60-60.4 Gy to the microscopically or macroscopically positive resection margins (R1/R2) region. Concurrent HT was performed at 40-42 ℃. Primary endpoint was LC. Acute and late toxicity, overall survival, cancer-specific survival (CSS), and progression-free survival (PFS) were also evaluated. RESULTS: 20 patients and 21 RBC were analyzed. Median re-RT dose was 50.4 Gy and a median of 11 HT fractions were applied. Re-RT+HT was well tolerated, with three patients who experienced a grade (G) 3 acute skin toxicity and no cases of ≥G3 late toxicity. With a median follow up of 24.7 months, two local relapses occurred. Ten patients experienced regional and/or distant disease progression. Five patients died, four of them from breast cancer. PFS was favorable in patients treated with re-RT+HT for the first recurrence with doses of 60 Gy. A trend towards better CSS was found in patients with negative or close margins and after doses of 60 Gy. CONCLUSION: Full-dose re-RT+HT for RBC is well tolerated, provides good LC, and seems to be more effective when applied at the time of the first relapse and after doses of 60 Gy. The registry will be continued for validation in a larger cohort and with longer follow-up.

Atypical ductal hyperplasia: Clinicopathologic factors are not predictive of upgrade after excisional biopsy.

INTRODUCTION: National Comprehensive Cancer Network (NCCN) guidelines currently recommend excisional biopsy for atypical ductal hyperplasia (ADH) diagnosed on core needle biopsy (CNB) due to the possibility of pathologic upgrade to breast cancer upon excisional biopsy. We aimed to quantify the current rate of upgrade and identify risk factors. METHODS: A retrospective review of women in the Legacy Health Care System with a diagnosis of ADH was performed for 2014 through 2015. Initial pathology and patient factors were reviewed for potential predictors of upgrade. RESULTS: 91 women with ADH were identified. 84 (92%) underwent excisional biopsy; 16 (19%) were upgraded to breast cancer. Those upgraded were significantly older than non-upgraded patients (64.6 versus 56.7 years, p < 0.01), and 15 (94%) had greater than one duct involved by ADH. CONCLUSION: The principal clinicopathologic factor associated with upgrade is increasing patient age, however this is not sufficiently predictive. Excisional biopsy in patients diagnosed with ADH on CNB should continue. Further study may provide an avenue for selective excisional biopsy in patients with ADH.

Intratumoral Heterogeneity in Ductal Carcinoma In Situ: Chaos and Consequence.

Ductal carcinoma in situ (DCIS) is a non-invasive proliferative growth in the breast that serves as a non-obligate precursor to invasive ductal carcinoma. The widespread adoption of screening mammography has led to a steep increase in the detection of DCIS, which now comprises approximately 20% of new breast cancer diagnoses in the United States. Interestingly, the intratumoral heterogeneity (ITH) that has been observed in invasive breast cancers may have been established early in tumorigenesis, given the vast and varied ITH that has been detected in DCIS. This review will discuss the intratumoral heterogeneity of DCIS, focusing on the phenotypic and genomic heterogeneity of tumor cells, as well as the compositional heterogeneity of the tumor microenvironment. In addition, we will assess the spatial heterogeneity that is now being appreciated in these lesions, and summarize new approaches to evaluate heterogeneity of tumor and stromal cells in the context of their spatial organization. Importantly, we will discuss how a growing understanding of ITH has led to a more holistic appreciation of the complex biology of DCIS, specifically its evolution and natural history. Finally, we will consider ways in which our knowledge of DCIS ITH might be translated in the future to guide clinical care for DCIS patients.

Ultraviolet Radiation Inhibits Mammary Carcinogenesis in an ER-Negative Murine Model by a Mechanism Independent of Vitamin D3.

Three decades ago, the Garlands postulated that vitamin D3 produced in the skin by ultraviolet radiation (UVR)-induced conversion of 7-dehydrocholesterol to pre-D3 has anticancer effects, thus triggering more than 9,500 publications on D3 and cancer. Here, we report that UVR treatment of transgenic mice of the well-established C3(1)/SV40 Tag mammary cancer model significantly inhibits both autochthonous carcinogenesis and allograft tumor growth, but in contrast neither dietary nor topical D3 influences mammary carcinogenesis in this specific mouse model. Furthermore, UVR's inhibitory effects occur irrespective of whether or not the treatment increases circulating D3 in the mice. The inhibitory effect of UVR on autochthonous tumors occurs at or before the stage of ductal carcinoma in situ. Our studies indicate clearly that UVR can exert D3-independent anticancer effects in C3(1)/SV40 Tag mice. Therefore, supplemental D3 may not mimic all possible beneficial effects of UVR, and uncovering non-D3-mediated mechanisms of UVR tumor inhibition may lead to novel strategies for cancer prevention. Cancer Prev Res; 11(7); 383-92. ©2018 AACR.

A Randomized Multicenter Phase II Study of Docosahexaenoic Acid in Patients with a History of Breast Cancer, Premalignant Lesions, or Benign Breast Disease.

Obesity, a cause of subclinical inflammation, is a risk factor for the development of postmenopausal breast cancer and is associated with poorer cancer outcomes. Docosahexaenoic acid (DHA), an omega-3 fatty acid, possesses anti-inflammatory properties. We hypothesized that treatment with DHA would reduce the expression of proinflammatory genes and aromatase, the rate-limiting enzyme for estrogen biosynthesis, in benign breast tissue of overweight/obese women. A randomized, placebo-controlled, double-blind phase II study of DHA given for 12 weeks to overweight/obese women with a history of stage I-III breast cancer, DCIS/LCIS, Paget's disease, or proliferative benign breast disease was carried out. In this placebo controlled trial, the primary objective was to determine whether DHA (1,000 mg by mouth twice daily) reduced breast tissue levels of TNFα. Secondary objectives included evaluation of the effect of DHA on breast tissue levels of COX-2, IL1ß, aromatase, white adipose tissue inflammation, and gene expression by RNA-seq. Red blood cell fatty acid levels were measured to assess compliance. From July 2013 to November 2015, 64 participants were randomized and treated on trial (32 women per arm). Increased levels of omega-3 fatty acids in red blood cells were detected following treatment with DHA (P < 0.001) but not placebo. Treatment with DHA did not alter levels of TNFα (P = 0.71), or other biomarkers including the transcriptome in breast samples. Treatment with DHA was overall well-tolerated. Although compliance was confirmed, we did not observe changes in the levels of prespecified biomarkers in the breast after treatment with DHA when compared with placebo. Cancer Prev Res; 11(4); 203-14. ©2018 AACRSee related editorial by Fabian and Kimler, p. 187.

Clinical risk score to predict likelihood of recurrence after ductal carcinoma in situ treated with breast-conserving surgery.

PURPOSE: A majority of women with ductal carcinoma in situ (DCIS) receive breast-conserving surgery (BCS) but then face a risk of ipsilateral breast tumor recurrence (IBTR) which can be either recurrence of DCIS or invasive breast cancer. We developed a score to provide individualized information about IBTR risk to guide treatment decisions. METHODS: Data from 2762 patients treated with BCS for DCIS at centers within the National Comprehensive Cancer Network (NCCN) were used to identify statistically significant non-treatment-related predictors for 5-year IBTR. Factors most associated with IBTR were estrogen-receptor status of the DCIS, presence of comedo necrosis, and patient age at diagnosis. These three parameters were used to create a point-based risk score. Discrimination of this score was assessed in a separate DCIS population of 301 women (100 with IBTR and 200 without) from Kaiser Permanente Northern California (KPNC). RESULTS: Using NCCN data, the 5-year likelihood of IBTR without adjuvant therapy was 9% (95% CI 5-12%), 23% (95% CI 13-32%), and 51% (95% CI 26-75%) in the low, intermediate, and high-risk groups, respectively. Addition of the risk score to a model including only treatment improved the C-statistic from 0.69 to 0.74 (improvement of 0.05). Cross-validation of the score resulted in a C-statistic of 0.76. The score had a c-statistic of 0.67 using the KPNC data, revealing that it discriminated well. CONCLUSIONS: This simple, no-cost risk score may be used by patients and physicians to facilitate preference-based decision-making about DCIS management informed by a more accurate understanding of risks.

Pilot study demonstrating metabolic and anti-proliferative effects of in vivo anti-oxidant supplementation with N-Acetylcysteine in Breast Cancer.

BACKGROUND: High oxidative stress as defined by hydroxyl and peroxyl activity is often found in the stroma of human breast cancers. Oxidative stress induces stromal catabolism, which promotes cancer aggressiveness. Stromal cells exposed to oxidative stress release catabolites such as lactate, which are up-taken by cancer cells to support mitochondrial oxidative phosphorylation. The transfer of catabolites between stromal and cancer cells leads to metabolic heterogeneity between these cells and increased cancer cell proliferation and reduced apoptosis in preclinical models. N-Acetylcysteine (NAC) is an antioxidant that reduces oxidative stress and reverses stromal catabolism and stromal-carcinoma cell metabolic heterogeneity, resulting in reduced proliferation and increased apoptosis of cancer cells in experimental models of breast cancer. The purpose of this clinical trial was to determine if NAC could reduce markers of stromal-cancer metabolic heterogeneity and markers of cancer cell aggressiveness in human breast cancer. METHODS: Subjects with newly diagnosed stage 0 and I breast cancer who were not going to receive neoadjuvant therapy prior to surgical resection were treated with NAC before definitive surgery to assess intra-tumoral metabolic markers. NAC was administered once a week intravenously at a dose of 150 mg/kg and 600 mg twice daily orally on the days not receiving intravenous NAC. Histochemistry for the stromal metabolic markers monocarboxylate transporter 4 (MCT4) and caveolin-1 (CAV1) and the Ki67 proliferation assay and TUNEL apoptosis assay in carcinoma cells were performed in pre- and post-NAC specimens. RESULTS: The range of days on NAC was 14-27 and the mean was 19 days. Post-treatment biopsies showed significant decrease in stromal MCT4 and reduced Ki67 in carcinoma cells. NAC did not significantly change stromal CAV1 and carcinoma TUNEL staining. NAC was well tolerated. CONCLUSIONS: NAC as a single agent reduces MCT4 stromal expression, which is a marker of glycolysis in breast cancer with reduced carcinoma cell proliferation. This study suggests that modulating metabolism in the tumor microenvironment has the potential to impact breast cancer proliferation.

Value of a short-term imaging follow-up after a benign result in a one-stop breast unit: Is it still useful?

INTRODUCTION: A short-term radiologic follow-up after a benign breast biopsy or fine needle aspiration (FNA) is recommended in many guidelines. However, the current trend is to reduce imaging investigations, radiation dose and costs. The objectives of this study were to evaluate the cancer detection rate at short-term follow-up and to estimate its cost. METHODS: We retrospectively assessed all consecutive patients referred to our 'one-stop' breast unit between 2004 and 2012, with a benign histological or cytological result and at least one short-term follow-up within 3-12 months after the initial diagnosis. We evaluated the number of cancers detected, as well as the mean cost to detect each cancer and per patient. RESULTS: About 1366 patients were eligible for this study. Ten patients were diagnosed with cancers (0.73%) at short-term follow-up; six of 10 were low-grade tumours or ductal carcinoma in situ. The cost for detecting one cancer was 19,043€, with mean cost per patient of 139€. CONCLUSION: The cancer detection rate at short-term follow-up after benign biopsy or FNA was low and was similar to that of most national screening programs. The cost of cancer detection appeared high, considering that most cancers were indolent. This suggests that radiologic follow-up could reasonably be carried out at a later point in time.

Secondary breast carcinoma after completely remitted chronic myeloid leukemia following targeted tyrosine kinase inhibitor therapy.

We describe a rare case of secondary breast carcinoma after chronic myeloid leukemia (CML) in a 56-year-old woman. The patient was treated with hydroxyurea and imatinib for CML and achieved complete remission (she has since been taking imatinib as the maintenance therapy). Four years later, the patient noticed a firm and painless lump in the left breast, which was diagnosed as ductal carcinoma in situ based on a percutaneous biopsy of the mass. Simple resection and sentinel lymph node biopsy of the left breast were then performed. Pathological studies revealed a medium-grade intraductal carcinoma, with local infiltration associated with invasive micropapillary carcinoma. She received adjuvant endocrine therapy with imatinib after surgery. Breast cancer secondary to CML (treated with imatinib and completely remitted) is extremely rare. This report provides evidence to assist in the diagnosis and treatment for this rare manifestation.

Identification of Patients With Documented Pathologic Complete Response in the Breast After Neoadjuvant Chemotherapy for Omission of Axillary Surgery.

Importance: A pathologic complete response (pCR; no invasive or in situ cancer) occurs in 40% to 50% of patients with HER2-positive (HER2+) and triple-negative (TN) breast cancer. The need for surgery if percutaneous biopsy of the breast after neoadjuvant chemotherapy (NCT) indicates pCR in the breast (hereinafter referred to as breast pCR) has been questioned, and appropriate management of the axilla in such patients is unknown. Objective: To identify patients among exceptional responders to NCT with a low risk for axillary metastases when breast pCR is documented who may be eligible for an omission of surgery clinical trial design. Design, Setting, and Participants: This prospective cohort study at a single-institution academic national comprehensive cancer center included 527 consecutive patients with HER2+/TN (T1/T2 and N0/N1) cancer treated with NCT followed by standard breast and nodal surgery from January 1, 2010, through December 31, 2014. Main Outcomes and Measures: Patients who achieved a breast pCR were compared with patients who did not based on subtype, initial ultrasonographic findings, and documented pathologic nodal status. Incidence of positive findings for nodal disease on final pathologic review was calculated for patients with and without pCR and compared using relative risk ratios with 95% CIs. Results: The analysis included 527 patients (median age, 51 [range, 23-84] years). Among 290 patients with initial nodal ultrasonography showing N0 disease, 116 (40.4%) had a breast pCR and 100% had no evidence of axillary lymph node metastases after NCT. Among 237 patients with initial biopsy-proved N1 disease, 69 of 77 (89.6%) with and 68 of 160 (42.5%) without a breast pCR had no evidence of residual nodal disease (P < .01). Patients without a breast pCR had a relative risk for positive nodal metastases of 7.4 (95% CI, 3.7-14.8; P < .001) compared with those with a breast pCR. Conclusions and Relevance: Breast pCR is highly correlated with nodal status after NCT, and the risk for missing nodal metastases without axillary surgery in this cohort is extremely low. These data provide the fundamental basis and rationale for management of the axilla in clinical trials of omission of cancer surgery when image-guided biopsy indicates a breast pCR.

Polyphenolics from mango (Mangifera indica L.) suppress breast cancer ductal carcinoma in situ proliferation through activation of AMPK pathway and suppression of mTOR in athymic nude mice.

The objective of this study was to assess the underlying mechanisms of mango polyphenol decreased cell proliferation and tumor volume in ductal carcinoma in situ breast cancer. We hypothesized that mango polyphenols suppress signaling along the AKT/mTOR axis while up-regulating AMPK. To test this hypothesis, mango polyphenols (0.8 mg gallic acid equivalents per day) and pyrogallol (0.2 mg/day) were administered for 4 weeks to mice xenografted with MCF10DCIS.com cells subcutaneously (n=10 per group). Tumor volumes were significantly decreased, both mango and pyrogallol groups displayed greater than 50% decreased volume compared to control. There was a significant reduction of phosphorylated protein levels of IR, IRS1, IGF-1R, and mTOR by mango; while pyrogallol significantly reduced the phosphorylation levels of IR, IRS1, IGF-1R, p70S6K, and ERK. The protein levels of Sestrin2, which is involved in AMPK-signaling, were significantly elevated in both groups. Also, mango significantly elevated AMPK phosphorylation and pyrogallol significantly elevated LKB1 protein levels. In an in vitro model, mango and pyrogallol increased reactive oxygen species (ROS) generation and arrested cells in S phase. In silico modeling indicates that pyrogallol has the potential to bind directly to the allosteric binding site of AMPK, inducing activation. When AMPK expression was down-regulated using siRNA in vitro, pyrogallol reversed the reduced expression of AMPK. This indicates that pyrogallol not only activates AMPK, but also increases constitutive protein expression. These results suggest that mango polyphenols and their major microbial metabolite, pyrogallol, inhibit proliferation of breast cancer cells through ROS-dependent up-regulation of AMPK and down-regulation of the AKT/mTOR pathway.

Sentinel lymph node biopsy and aberrant lymphatic drainage in recurrent breast cancer: Findings likely to change treatment decisions.

BACKGROUND AND OBJECTIVES: It is not clear whether sentinel lymph node biopsy (SLNB) can be applied to patients with a second breast cancer or recurrence occurring at previously treated breast. The purpose of this study was to assess the feasibility of SLNB procedure in patients with recurrent breast cancer. METHODS: Patients with non-metastatic recurrent N0 breast cancer at ipsilateral breast were included. Patients were grouped according to their initial breast, axilla, and overall surgery. Presence of drainage and its pattern as well as SLNB success rate and overall axillary involvement rates were assessed. Findings were compared. RESULTS: Out of 75 patients, mean age was 52.5 years and disease-free interval was 82 (9-312) months. Lymphatic drainage was successful in 42 (56%) patients. Drainage positivity was more frequent in patients who were previously treated with SLNB (82.6%) than in patients who underwent axillary lymph node dissection (ALND) (44.2%; P = 0,002). Aberrant lymphatic drainage was detected in 64.3% of drainage positive patients. Success rate of reoperative SLNB was 92.9%. Adjuvant treatment plan was altered in 12 (16%) patients. In 15 patients, negative SLNB prevented axillary dissection. CONCLUSIONS: Reoperative SLNB seems to be technically feasible in N0 recurrent breast cancer patients. It may further avoid unnecessary ALND and lead changes in adjuvant treatment plans. J. Surg. Oncol. 2016;114:796-802. © 2016 2016 Wiley Periodicals, Inc.