Paget's Presentation of High-Grade Ductal Carcinoma In Situ (DCIS) in a Very Young Female With Breast Cancer 2 (BRCA2) Mutation.

This is a case of a previously healthy 29-year-old female with erythema and skin excoriations of the left breast nipple-areolar complex (NAC). After a repeat trial and failure of topical hydrocortisone, a diagnostic mammogram and nipple biopsy revealed Paget's disease (PD) of the nipple with ductal carcinoma in situ (DCIS). A subsequent genetic analysis found a breast cancer 2 (BRCA2) gene mutation. Treatment consisted of a left breast skin-sparing simple mastectomy with sentinel lymph node (SLN) biopsy and immediate tissue expander placement for implant reconstruction. Further management involved right breast short-interval surveillance with annual mammography and magnetic resonance imaging (MRI) with the possibility of prophylactic surgery along with oophorectomy after childbearing.

Effects of vitamin D supplementation on a deep learning-based mammographic evaluation in SWOG S0812.

Deep learning-based mammographic evaluations could noninvasively assess response to breast cancer chemoprevention. We evaluated change in a convolutional neural network-based breast cancer risk model applied to mammograms among women enrolled in SWOG S0812, which randomly assigned 208 premenopausal high-risk women to receive oral vitamin D3 20 000 IU weekly or placebo for 12 months. We applied the convolutional neural network model to mammograms collected at baseline (n = 109), 12 months (n = 97), and 24 months (n = 67) and compared changes in convolutional neural network-based risk score between treatment groups. Change in convolutional neural network-based risk score was not statistically significantly different between vitamin D and placebo groups at 12 months (0.005 vs 0.002, P = .875) or at 24 months (0.020 vs 0.001, P = .563). The findings are consistent with the primary analysis of S0812, which did not demonstrate statistically significant changes in mammographic density with vitamin D supplementation compared with placebo. There is an ongoing need to evaluate biomarkers of response to novel breast cancer chemopreventive agents.

Adenoid Cystic Carcinoma of the Breast: Two Case Reports.

In this series of case reports, we present two women diagnosed with rare cancer, adenoid cystic carcinoma (ACC) of the breast. Though this neoplasm has a relatively favorable prognosis, more information regarding its pathophysiology, response to variable treatments, and long-term prognosis is needed. The objective of our case series is to present the medical decisions and clinical courses of a 50-year-old female and a 79-year-old female with ACC of the breast. Through ongoing shared knowledge from cases like ours and further experimental research, a more reliable diagnostic and treatment algorithm can be substantiated.

Randomized Double-Blind Placebo-Controlled Biomarker Modulation Study of Vitamin D Supplementation in Premenopausal Women at High Risk for Breast Cancer (SWOG S0812).

Observational studies have reported an inverse association between vitamin D intake and breast cancer risk. We examined whether vitamin D supplementation in high-risk premenopausal women reduces mammographic density (MD), an established breast cancer risk factor. We conducted a multicenter randomized double-blind placebo-controlled trial in premenopausal women at high risk for breast cancer [5-year risk ≥ 1.67%, lifetime risk ≥ 20%, lobular carcinoma in situ, prior stage 0-II breast cancer, hereditary breast cancer syndrome, or high MD (heterogeneously/extremely dense)], with a baseline serum 25-hydroxyvitamin D [25(OH)D] ≤ 32 ng/mL. Participants were randomized to 12 months of vitamin D3 20,000 IU/week or matching placebo. The primary endpoint was change in MD from baseline to 12 months using the Cumulus technique. Secondary endpoints included serial blood biomarkers [25(OH)D, 1,25-dihydroxyvitamin D (1,25(OH)D), insulin-like growth factor (IGF)-1, IGF-binding protein-3] and MD change at 24 months. Among 208 women randomized, median age was 44.6 years, 84% were white, 33% had baseline 25(OH)D < 20 ng/mL, and 78% had high baseline MD. Comparing the active and placebo groups at 12 months, MD changes were small and did not significantly differ. Mean MD changes at 12 and 24 months were -0.3% and -1.2%, respectively, in the active arm and +1.5% and +1.6% with placebo (P > 0.05). We observed a mean change in serum 25(OH)D of +18.9 versus +2.8 ng/mL (P < 0.01) and IGF-1 of -9.8 versus -1.8 ng/mL (P = 0.28), respectively. At 12 months, MD was positively correlated with serum IGF-1 and IGF-1/IGFBP-3 (P < 0.01). This trial does not support the use of vitamin D supplementation for breast cancer risk reduction.

Resveratrol induces prostate cancer cell entry into s phase and inhibits DNA synthesis.

Resveratrol has an apoptotic effect on a variety of cancer cells. Changes in cell cycle regulatory processes contributing to the antiproliferative effect of resveratrol remain largely unknown. Our studies revealed that, in androgen-sensitive LNCaP cells, the effect of resveratrol on DNA synthesis varied dramatically depending on the concentration and the duration of treatment. In 1-h-treated cells, resveratrol showed only an inhibitory effect on DNA synthesis, which increased with increasing concentration (IC50 = 20 microM). However, when treatment duration was extended to 24 h, we observed a dual effect of resveratrol on DNA synthesis. At 5 to 10 microM it caused a 2- to 3-fold increase in DNA synthesis, and at > or =15 microM, it inhibited DNA synthesis. The increase in DNA synthesis was seen only in LNCaP cells, but not in androgen-independent DU145 prostate cancer cells or in NIH3T3 fibroblast cells. The resveratrol-induced increase in DNA synthesis was associated with enrichment of LNCaP cells in S phase, and a concurrent decrease in nuclear p21Cipl and p27Kip1 levels. Furthermore, consistent with the entry of LNCaP cells into S phase, there was a dramatic increase in nuclear Cdk2 activity associated with both cyclin A and cyclin E. Taken together, our observations indicate that LNCaP cells, treated with resveratrol, are induced to enter into S phase, but subsequent progression through S phase is limited by the inhibitory effect of resveratrol on DNA synthesis, particularly at concentrations above 15 microM. Therefore, this unique ability of resveratrol to exert opposing effects on two important processes in cell cycle progression, induction of S phase and inhibition of DNA synthesis, may be responsible for its apoptotic and antiproliferative effects.

Effects of surgical gloves on postoperative peritoneal adhesions and cytokine expression in a rat model.

BACKGROUND: Postoperative intraperitoneal adhesions are a major cause of morbidity. We studied the effects of synthetic and latex gloves, and their powders, on postoperative adhesions and cytokine expression in a rat model. METHODS: Rats underwent laparotomy and cecal abrasion. Rats were grouped based on the glove type used: synthetic powder-free (SPF), synthetic powdered (SP), latex powder-free (LPF), and latex powdered (LP). Serum cytokine (tumor necrosis factor [TNF], interleukin-1 [IL-1], and IL-6) levels were measured. Animals were killed and peritoneal adhesions were graded. RESULTS: The SPF group had no adhesions. Adhesions were increased similarly in the SP and LPF groups, and further increased in the LP group. Postoperative serum cytokine levels showed a similar pattern of increases. CONCLUSIONS: The presence of latex or powder on surgical gloves promoted increased adhesions. Serum cytokine levels correlated with the degree of adhesion formation. Strategies to use latex-free, powder-free gloves and/or limit cytokine expression may decrease peritoneal adhesions in the clinical setting.

Implementation of an oncology exercise and wellness rehabilitation program to enhance survivorship: the Beaumont Health System experience.

We developed a multidisciplinary approach to oncology rehabilitation by setting up a physical therapy screening program in a dedicated multidisciplinary clinic to improve survivorship care in the community oncology setting. In June 2011, an oncology rehabilitation program was launched as part of the overall survivorship program to provide patients with an introduction to cancer services, consultation with multiple clinicians, education about their diagnoses, and recommendation for rehabilitation services during or after treatment. The consultation was in conjunction with specialists at the multidisciplinary clinics that were already established within the organization. A dedicated and trained oncology physical therapist participated in the comprehensive multidisciplinary discussion. From the beginning of the program in June 2011 until December 2012, 288 patients (231 women and 57 men) entered the oncology exercise and wellness rehabilitation program. The establishment of the program improved the quality of care for cancer patients as demonstrated by the number of patients screened before treatment recommendations. The program also served the need for continued health and wellness for those in survivorship.

Comparison of lymphedema in patients with axillary lymph node dissections to those with sentinel lymph node biopsy followed by immediate and delayed ALND.

PURPOSE: The purpose of the study was to show that delayed axillary lymph node dissection (ALND) has higher rates of lymphedema compared with immediate ALND, using data from NSABP-B32 at Beaumont Hospital. METHOD: NSABP B-32 at Beaumont had 207 patients with follow-up data on 199 patients, randomizing clinically negative axilla to sentinel lymph node biopsy (SLNB)+ALND (GrA N=98), and SLNB+cytology±ALND (GrB N=101). All patients had preoperative volumetric arm measurements and only node negatives had routine postoperative measurements assessing lymphedema for 36 months. We contacted node-positive patients for postoperative measurements for this study. Twenty-four and 15 cytology-positive patients had SLNB+ALND in GrA and GrB, respectively (SubGrA1 N=24; SubGrB1 N=15). Fourteen hematoxylin and eosin-positive patients had delayed ALND (SubGrB2a N=14). RESULTS: Lymphedema rate for node-positive SLNB+ALND was 10.3% [SubGrA1 (3/24)+SubGrB1 (1/15)=4/39] and node-negative SLNB+ALND was 6.8% (SubGrA2=5/74). Lymphedema was 14.3% for delayed ALND in SubGrB2a (2 of 14) and 0% for 72 SLNBs in SubGrB2b. Our study comparing immediate and delayed ALND lymphedema was not statistically significant (10.3% vs. 14.3%, P=0.65). Comparing node-negative ALND (SubGrA2= 5/74=6.8%) to node-positive ALND (A1+B1+B2a=6/53=11.3%) was not statistically significant (P=0.52). Comparing lymphedema for node-negative ALND (SubGrA2) to SLNB (SubGrB2b) only approached significance (6.8% vs. 0%, P=0.058). CONCLUSIONS: The rate of lymphedema was higher in delayed ALND but not statistically significant. Comparison, however, is difficult, given the limited sample size. We urge the other centers of NSABP-B32 to validate this, by contacting the node-positive patients for measurements. The lymphedema rate for SLNB alone was 0% and approached statistical significance when compared with node-negative ALND.

Sentinel lymph node biopsy in contralateral prophylactic mastectomy: are we overtreating? Experience at a tertiary care hospital.

OBJECTIVE: Use of routine sentinel lymph node biopsy (SLNB) in contralateral prophylactic mastectomy (CPM) is controversial. This retrospective study was undertaken to determine the frequency of SLNB in CPM at a community hospital and its utility as a guide to patient decision making. METHODS: Between 2007 and 2009, 170 patients underwent CPM at a suburban, tertiary care facility. The CPM was either immediate or delayed, or was for ipsilateral recurrent breast cancer. Thirty-seven (21.8%) of 170 patients had SLNB performed with CPM. The mastectomy specimens underwent standard pathologic evaluation by using intraoperative touch preparation cytology and postoperative hematoxylin and eosin staining and immunohistochemistry. RESULTS: No patients who underwent SLNB had positive nodes on touch preparation or final hematoxylin and eosin staining (0/37 [0%]). Fourteen (8.2%) of 37 patients had additional nodes identified in the specimens. These were either axillary tail or intramammary nodes. The median number of SLNs removed was 2 (range, 1-5), none of these were positive. There were 3 incidental cancers diagnosed on final pathology. Two invasive cancers (T1a and grade I) and 1 ductal carcinoma in situ were identified. SLNB was only performed on the patient with DCIS. Neither SLNB nor subsequent axillary lymph node dissection was performed in the invasive cancers. CONCLUSIONS: SLNB was performed in 37 (21.8%) of patients who underwent CPM in a community hospital. Only 3 (1.76%) of 170 patients who underwent CPM had findings on final pathology that would have justified axillary staging. This correlates with other published data regarding SLNB in CPM. Because SLNB is associated with significant morbidity, guidelines for SLNB in prophylactic mastectomy need to be established so to avoid overtreatment.

Tamoxifen malabsorption after Roux-en-Y gastric bypass surgery: case series and review of the literature.

Roux-en-Y gastric bypass is a gastric reduction duodenal switch with a combination of restrictive and malabsorptive procedures. It is the most common gastric bypass procedure performed in the United States. Malabsorption causing nutritional deficiencies does occur, yet a PubMed literature search (1955-2009) returned no reports of malabsorption of anticancer agents after gastric bypass. To our knowledge, this is the first report of three cases of malabsorption of the anticancer agent tamoxifen after this procedure. The first patient was a 58-year-old woman who underwent Roux-en-Y bypass for morbid obesity. Two years later, she developed estrogen receptor-positive ductal carcinoma in situ of the breast, underwent lumpectomy and irradiation, and tamoxifen was started. Two years after that, she presented with concerns of potential malabsorption of the drug. Her plasma tamoxifen level was 28 ng/ml, which was below the lower limit of the therapeutic range (77-274 ng/ml for 10-30-mg/day regimens). The second patient was a 51-year-old woman who sought medical advice on risk reduction for breast cancer after receiving a diagnosis of atypical ductal hyperplasia of the breast. She also had a history of morbid obesity and underwent Roux-en-Y bypass. Tamoxifen was started to reduce her risk of breast cancer; her plasma tamoxifen level was subtherapeutic at 14 ng/ml. The third patient was a 53-year-old woman with estrogen receptor-positive breast cancer who underwent lumpectomy and was prescribed anastrozole, an aromatase inhibitor. She also underwent Roux-en-Y bypass for morbid obesity. As she experienced adverse effects while receiving anastrozole, the drug was discontinued, and tamoxifen 20 mg/day was started. Her tamoxifen plasma level was 52 ng/ml. Therefore, her tamoxifen dosage was increased to 20 mg twice/day. Six weeks later, her tamoxifen level was 120 ng/ml (therapeutic range 95-520 ng/ml for the increased dosage). These three cases suggest that steady-state serum tamoxifen levels should be evaluated in patients who have undergone Roux-en-Y gastric bypass. Until adequate data suggest otherwise, parenteral anticancer alternatives should be considered when systemic therapy is needed in a patient with malabsorption.