Alternating 17ß-Estradiol and Aromatase Inhibitor Therapies Is Efficacious in Postmenopausal Women with Advanced Endocrine-Resistant ER+ Breast Cancer.

PURPOSE: Strategies to implement estrogen therapy for advanced estrogen receptor-positive (ER+) breast cancer are underdeveloped. Preclinical data suggest that cycling treatment with 17ß-estradiol followed by estrogen deprivation can control tumor growth long-term. PATIENTS AND METHODS: Postmenopausal women with advanced ER+/HER2- breast cancer with recurrence or progression on ≥ 1 antiestrogen or aromatase inhibitor (AI)-based therapy were eligible. Patients received 17ß-estradiol (2 mg orally, three times a day) for 8 weeks followed by AI (physician's choice) for 16 weeks, alternating treatments on an 8-week/16-week schedule until disease progression. Patients then optionally received continuous single-agent treatment until a second instance of disease progression. Endpoints included 24-week clinical benefit and objective response per RECIST, and tumor genetic alterations. RESULTS: Of 19 evaluable patients, clinical benefit rate was 42.1% [95% confidence interval (CI), 23.1%-63.9%] and objective response rate (ORR) was 15.8% (95% CI, 5.7%-37.9%). One patient experienced a grade 3 adverse event related to 17ß-estradiol. Among patients who received continuous single-agent treatment until a second instance of disease progression, clinical benefit was observed in 5 of 12 (41.7%) cases. Tumor ER (ESR1) mutations were found by whole-exome profiling in 4 of 7 (57.1%) versus 2 of 9 (22.2%) patients who did versus did not experience clinical benefit from alternating 17ß-estradiol/AI therapy. The only two patients to experience objective responses to initial 17ß-estradiol had tumor ESR1 mutations. CONCLUSIONS: Alternating 17ß-estradiol/AI therapy may be a promising treatment for endocrine-refractory ER+ breast cancer, including following progression on CDK4/6 inhibitors or everolimus. Further study is warranted to determine whether the antitumor activity of 17ß-estradiol differs according to ESR1 mutation status.

Outcomes of a Multidisciplinary Team in the Management of Patients with Early-Stage Breast Cancer Undergoing Neoadjuvant Chemotherapy at a Community Cancer Center.

Background: The utilization of neoadjuvant chemotherapy (NAC) remains highly variable in clinical practice. The implementation of NAC requires coordination of handoffs between a multidisciplinary team (MDT). This study aims to assess the outcomes of an MDT in the management of early-stage breast cancer patients undergoing neoadjuvant chemotherapy at a community cancer center. Methods: We conducted a retrospective case series on patients receiving NAC for early-stage operable or locally advanced breast cancer coordinated by an MDT. Outcomes of interest included the rate of downstaging of cancer in the breast and axilla, time from biopsy to NAC, time from completion of NAC to surgery, and time from surgery to radiation therapy (RT). Results: Ninety-four patients underwent NAC; 84% were White and mean age was 56.5 yrs. Of them, 87 (92.5%) had clinical stage II or III cancer, and 43 (45.8%) had positive lymph nodes. Thirty-nine patients (42.9%) were triple negative, 28 (30.8%) were human epidermal growth factor receptor (HER-2)+, and 24 (26.2%) were estrogen receptor (ER) +HER-2-. Of 91 patients, 23 (25.3%) achieved pCR; 84 patients (91.4%) had downstaging of the breast tumor, and 30 (33%) had axillary downstaging. The median time from diagnosis to NAC was 37.5 days, the time from completion of NAC to surgery was 29 days, and the time from surgery to RT was 49.5 days. Conclusions: Our MDT provided timely, coordinated, and consistent care for patients with early-stage breast cancer undergoing NAC as evidenced by time to treatment outcomes consistent with recommended national trends.

Mode of Detection of Second Events in Routine Surveillance of Early Stage Breast Cancer Patients.

INTRODUCTION: NCCN and ASCO guidelines recommend breast cancer (BC) follow-up to include clinical breast examination (CBE) every 6 months and annual mammography (AM) for 5 years. Given limited data to support CBE, we evaluated the modes of detection (MOD) of BC-events in a contemporary practice. METHODS: We conducted a retrospective review of registry patients with early stage BC (DCIS, Stage I or II) diagnosed between 2010 and 2015 with at least 5 years of follow-up. Second events were defined as malignant (contralateral primary, ipsilateral breast tumor recurrence (IBTR), chest wall recurrence, regional node recurrence or distant relapse) or benign. MOD was categorized as patient complaint, clinical examination or breast imaging. RESULTS: Sixty-three of 351 BC patients experienced second events. 15 had BC malignant events, including 4 distant disease, 5 contralateral primary, and 3 IBTR. 7/8 of IBTR and contralateral primary BC were AM detected. Patient complaints identified 4/4 distant relapses. Clinical exam identified 2/2 chest wall recurrences in post-mastectomy patients. CONCLUSIONS: Only 2.8% (10/351) of early stage BC patients experienced recurrence during 5 years of follow-up. AM was the predominate MOD of both IBTR and new contralateral primary following breast conserving therapy. Patient complaints prompted evaluation for distant disease. Provider CBE was MOD in only 2/351, 0.6% 95% CI (2.1%-0.1%) of patients as chest wall recurrences postmastectomy. Given modern enhancements to imaging and lower recurrence rates, this data encourages the reassessment of guidelines for every 6-month CBE and provides basis to study telehealth in survivorship care.

Experiences of individuals with a variant of uncertain significance on genetic testing for hereditary cancer risks: a mixed method systematic review.

The expansion of Multi-Gene Panel Testing (MGPT) has led to increased detection of variants of uncertain significance (VUS) among individuals with personal or family history of cancer. However, having a VUS result can impact on emotional and psychological wellbeing and cause challenges for non-geneticist healthcare providers. The purpose of this mixed methods systematic review was to examine what is currently known about the experiences of individuals with a VUS on genetic testing for inherited cancer susceptibility. The initial search was conducted in June 2020 using PUBMED, CINAHL, Web of Science, and PsychInfo according to the Joanna Briggs methodology for systematic reviews. A total of 18 studies met the inclusion criteria. Studies included in this review identified a range of emotional reactions to a VUS result, a general lack of understanding of a VUS result and its implications, frustration with a lack of healthcare provider knowledge, and a need for clear communication with healthcare providers. This review identified critical gaps in current knowledge to guide genetic counseling praxis, specifically in the knowledge of communication patterns and methods of improving communication with healthcare providers and family members and preferred risk management strategies. This will help to improve the counseling process and the management of care during and after genetic testing.

Interindividual variation contributes to differential PCB 126 induced gene expression in primary breast epithelial cells and tissues.

PCB 126 is a pervasive, dioxin-like chemical pollutant which can activate the aryl hydrocarbon receptor (AhR). Despite being banned from the market, PCB 126 can be detected in breast milk to this day. The extent to which interindividual variation impacts the adverse responses to this chemical in the breast tissue remains unclear. This study aimed to investigate the impact of 3 nM PCB 126 on gene expression in a panel of genetically diverse benign human breast epithelial cell (HBEC) cultures and patient derived breast tissues. Six patient derived HBEC cultures were treated with 3 nM PCB 126. RNAseq was used to interrogate the impact of exposure on differential gene expression. Gene expression changes from the top critical pathways were confirmed via qRT-PCR in a larger panel of benign patient derived HBEC cultures, as well as in patient-derived breast tissue explant cultures. RNAseq analysis of HBEC cultures revealed a signature of 144 genes significantly altered by 3 nM PCB 126 treatment. Confirmation of 8 targets using a panel of 12 HBEC cultures and commercially available breast cell lines demonstrated that while the induction of canonical downstream target gene, CYP1A1, was consistent across our primary HBECs, other genes including AREG, S100A8, IL1A, IL1B, MMP7, and CCL28 exhibited significant variability across individuals. The dependence on the activity of the aryl hydrocarbon receptor was confirmed using inhibitors. PCB 126 can induce significant and consistent changes in gene expression associated with xenobiotic metabolism in benign breast epithelial cells. Although the induction of most genes was reliant on the AhR, significant variability was noted between genes and individuals. These data suggest that there is a bifurcation of the pathway following AhR activation that contributes to the variation in interindividual responses.

Insulin resistance and weight gain in women treated for early stage breast cancer.

PURPOSE: Both weight gain and insulin resistance have been associated with poorer prognosis in women receiving adjuvant therapy for early stage breast cancer, however, interactions between weight gain and insulin resistance have not been explored longitudinally throughout the breast cancer treatment continuum. METHODS: One hundred non-diabetic women with early stage breast cancer receiving adjuvant chemotherapy and /or hormonal therapy were enrolled in this prospective, observational study. Metrics of weight, body composition (BMI, waist/hip circumference ratio (WHR)), and cardiometabolic health (fasting insulin, glucose and triglycerides) were obtained prior to adjuvant therapy (baseline) and repeated 6, 12, and 24 months post-diagnosis. Insulin resistance was calculated using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). RESULTS: Complete data were available for 95 participants. Compared to baseline, body weight was significantly higher at the 12-month time-point (75.3 ± 15.7 vs. 76.2 ± 16.7, p = 0.03), however there was no difference in waist circumference (p = 0.96) or WHR (p = 0.52). HOMA-IR tended to increase 6 months after diagnosis (2.36 ± 2.17 vs. 2.70 ± 2.83, p = 0.06), largely driven by adverse responses in patients treated with chemotherapy (mean change + 0.53 (chemotherapy) vs - 0.64 (no chemotherapy), p = 0.005). Despite 12-month weight gain, the 6-month increase in HOMA-IR was fully abrogated 12 months after diagnosis. CONCLUSION: Breast cancer patients experience small but significant weight gain in the year following diagnosis, and those who receive chemotherapy experience significant short-term metabolic impairments suggestive of insulin resistance. While the acute insulin resistance appears to attenuate over time, the long-term ramifications are unclear and may help explain weight gain in this population.

Inter-Individual Variation in Response to Estrogen in Human Breast Explants.

Exposure to estrogen is strongly associated with increased breast cancer risk. While all women are exposed to estrogen, only 12% are expected to develop breast cancer during their lifetime. These women may be more sensitive to estrogen, as rodent models have demonstrated variability in estrogen sensitivity. Our objective was to determine individual variation in expression of estrogen receptor (ER) and estrogen-induced responses in the normal human breast. Human breast tissue from female donors undergoing reduction mammoplasty surgery were collected for microarray analysis of ER expression. To examine estrogen-induced responses, breast tissue from 23 female donors were cultured ex- vivo in basal or 10 nM 17ß-estradiol (E2) media for 4 days. Expression of ER genes (ESR1 and ESR2) increased significantly with age. E2 induced consistent increases in global gene transcription, but expression of target genes AREG, PGR, and TGFß2 increased significantly only in explants from nulliparous women. E2-treatment did not induce consistent changes in proliferation or radiation induced apoptosis. Responses to estrogen are highly variable among women and not associated with levels of ER expression, suggesting differences in intracellular signaling among individuals. The differences in sensitivity to E2-stimulated responses may contribute to variation in risk of breast cancer.

Metrics of Diabetes Risk Are Only Minimally Improved by Exercise Training in Postmenopausal Breast Cancer Survivors.

CONTEXT: Insulin resistance is a risk factor for breast cancer recurrence. How exercise training changes fasting and postglucose insulin resistance in breast cancer survivors is unknown. OBJECTIVE: To evaluate exercise-induced changes in postglucose ingestion insulin concentrations, insulin resistance, and their associations with cancer-relevant biomarkers in breast cancer survivors. SETTING: The University of Massachusetts Kinesiology Department. PARTICIPANTS: 15 postmenopausal breast cancer survivors not meeting the physical activity guidelines (150 min/week of exercise). INTERVENTION: A supervised 12-week aerobic exercise program (60 min/day, 3-4 days/week). MAIN OUTCOME MEASURES: Postglucose ingestion insulin was determined by peak insulin and area under the insulin curve (iAUC) during a 5-sample oral glucose tolerance test. Insulin sensitivity was estimated from the Matsuda composite insulin sensitivity index (C-ISI). Changes in fitness and body composition were determined from submaximal VO2peak and dual energy X-ray absorptiometry. RESULTS: Participants averaged 156.8 ± 16.6 min/week of supervised exercise. Estimated VO2peak significantly increased (+2.8 ± 1.4 mL/kg/min, P < .05) and body weight significantly decreased (-1.1 ± 0.8 kg, P < .05) following the intervention. There were no differences in fasting insulin, iAUC, C-ISI, or peak insulin following the intervention. Insulin was only significantly lower 120 min following glucose consumption (68.8 ± 34.5 vs 56.2 ± 31.9 uU/mL, P < .05), and there was a significant interaction with past/present aromatase inhibitor (AI) use for peak insulin (-11.99 non-AI vs +13.91 AI uU/mL) and iAUC (-24.03 non-AI vs +32.73 AI uU/mL). CONCLUSIONS: Exercise training had limited overall benefits on insulin concentrations following glucose ingestion in breast cancer survivors but was strongly influenced by AI use.

Gene expression signature of atypical breast hyperplasia and regulation by SFRP1.

BACKGROUND: Atypical breast hyperplasias (AH) have a 10-year risk of progression to invasive cancer estimated at 4-7%, with the overall risk of developing breast cancer increased by ~ 4-fold. AH lesions are estrogen receptor alpha positive (ERα+) and represent risk indicators and/or precursor lesions to low grade ERα+ tumors. Therefore, molecular profiles of AH lesions offer insights into the earliest changes in the breast epithelium, rendering it susceptible to oncogenic transformation. METHODS: In this study, women were selected who were diagnosed with ductal or lobular AH, but no breast cancer prior to or within the 2-year follow-up. Paired AH and histologically normal benign (HNB) tissues from patients were microdissected. RNA was isolated, amplified linearly, labeled, and hybridized to whole transcriptome microarrays to determine gene expression profiles. Genes that were differentially expressed between AH and HNB were identified using a paired analysis. Gene expression signatures distinguishing AH and HNB were defined using AGNES and PAM methods. Regulation of gene networks was investigated using breast epithelial cell lines, explant cultures of normal breast tissue and mouse tissues. RESULTS: A 99-gene signature discriminated the histologically normal and AH tissues in 81% of the cases. Network analysis identified coordinated alterations in signaling through ERα, epidermal growth factor receptors, and androgen receptor which were associated with the development of both lobular and ductal AH. Decreased expression of SFRP1 was also consistently lower in AH. Knockdown of SFRP1 in 76N-Tert cells resulted altered expression of 13 genes similarly to that observed in AH. An SFRP1-regulated network was also observed in tissues from mice lacking Sfrp1. Re-expression of SFRP1 in MCF7 cells provided further support for the SFRP1-regulated network. Treatment of breast explant cultures with rSFRP1 dampened estrogen-induced progesterone receptor levels. CONCLUSIONS: The alterations in gene expression were observed in both ductal and lobular AH suggesting shared underlying mechanisms predisposing to AH. Loss of SFRP1 expression is a significant regulator of AH transcriptional profiles driving previously unidentified changes affecting responses to estrogen and possibly other pathways. The gene signature and pathways provide insights into alterations contributing to AH breast lesions.

Bisphenol-A in breast adipose tissue of breast cancer cases and controls.

We evaluated whether bisphenol-A (BPA) could be quantified in breast adipose tissue samples provided by 36 breast cancer mastectomy patients and 14 reduction mammoplasty patients. Samples of breast adipose tissue were collected and BPA concentration was quantified using HPLC-ESI-MS/MS. BPA was detectable above the limit of quantitation of 0.38 ng/g in 30.6% of samples. BPA concentrations varied within- and between breasts and were similar between cases and controls (0.39 vs 0.41 ng/g, p = 0.74).

'No Pink Ribbons': How Women's Lived Experiences With Breast Atypia Inform Decisions Involving Risk-Reducing Medications.

PURPOSE: Atypical hyperplasia (AH) is associated with a nearly 4-fold elevation of lifetime risk for breast cancer, and lobular carcinoma in situ (LCIS) is associated with a 7- to 8-fold risk. Women with AH/LCIS make numerous decisions in the course of treatment, including whether to take a risk-reducing medication, an option relatively few women pursue. We explored women's decision-making processes through patient narratives in an effort to inform decision supports for AH/LCIS. METHODS: We conducted in-depth interviews with 20 English-speaking women with AH/LCIS and no subsequent diagnosis of invasive breast cancer who had enrolled in the Rays of Hope Center for Breast Cancer Research patient registry between April 5, 2012, and March 31, 2016. Interviews were audiotaped, professionally transcribed, and qualitatively analyzed using thematic qualitative content analysis. RESULTS: We identified three major narrative themes: 1) experiences with medical care; 2) decision-making; and 3) making sense of AH/LCIS. Each major theme had several subthemes, many of which map onto existing decisional theories and heuristics. Subthemes included the impact of life context on diagnosis meaning, emotional responses, changes in self-concept and body image, and understanding of the risk-benefit of risk-reducing medications. CONCLUSIONS: This narrative analysis offers important insights into how lived experience may influence decision-making for women with AH/LCIS. Decision supports that focus not only on analytic decisional processes, but also patients' subjectivities and decisional heuristics, could prove useful for women and their health care providers.

Individual-specific variation in the respiratory activities of HMECs and their bioenergetic response to IGF1 and TNFα.

Metabolic reprograming is a hallmark of cancer cells. However, the roles of pre-existing differences in normal cells metabolism toward cancer risk is not known. In order to assess pre-existing variations in normal cell metabolism, we have quantified the inter-individual variation in oxidative metabolism of normal primary human mammary epithelial cells (HMECs). We then assessed their response to selected cytokines such as insulin growth factor 1 (IGF1) and tumor necrosis factor alpha (TNFα), which are associated with breast cancer risk. Specifically, we compared the oxidative metabolism of HMECs obtained from women with breast cancer and without cancer. Our data show considerable inter-individual variation in respiratory activities of HMECs from different women. A bioenergetic parameter called pyruvate-stimulated respiration (PySR) was identified as a key distinguishing feature of HMECs from women with breast cancer and without cancer. Samples showing PySR over 20% of basal respiration rate were considered PySR+ve and the rest as PySR-ve . By this criterion, HMECs from tumor-affected breasts (AB) and non-tumor affected breasts (NAB) of cancer patients were mostly PySR-ve (88% and 89%, respectively), while HMECs from non-cancer patients were mostly PySR+ve (57%). This suggests that PySR-ve/+ve phenotypes are individual-specific and are not caused by field effects due to the presence of tumor. The effects of IGF1 and TNFα treatments on HMECs revealed that both suppressed respiration and extracellular acidification. In addition, IGF1 altered PySR-ve/+ve phenotypes. These results reveal individual-specific differences in pyruvate metabolism of normal breast epithelial cells and its association with breast cancer risk.

Weight gain following breast cancer diagnosis: Implication and proposed mechanisms.

Weight gain occurs in the majority of women following breast cancer treatment. An overview of studies describing weight gain amongst women treated with early to modern chemotherapy regimens is included. Populations at higher risk include women who are younger, closer to ideal body weight and who have been treated with chemotherapy. Weight gain ranges between 1 to 5 kg, and may be associated with change in body composition with gain in fat mass and loss in lean body mass. Women are unlikely to return to pre-diagnosis weight. Possible mechanisms including inactivity and metabolic changes are explored. Potential interventions are reviewed including exercise, dietary changes and pharmacologic agents. Although breast cancer prognosis does not appear to be significantly impacted, weight gain has negative consequences on quality of life and overall health. Future studies should explore change in body composition, metabolism and insulin resistance. Avoiding weight gain in breast cancer survivors following initial diagnosis and treatment should be encouraged.

Using quality oncology practice initiative metrics for physician incentive compensation.

PURPOSE: To demonstrate the use of American Society of Clinical Oncology (ASCO) Quality Oncology Practice Initiative (QOPI) measures as part of a financial incentive plan for an academic health center-based hematology-oncology division. METHODS: An 11-member QOPI-certified hematology-oncology division participated in a pilot variable compensation (VC) plan with group-specific targets selected based on prior below-average performance. Twenty percent of overall VC was linked to success in two QOPI categories: completion of treatment summaries within 90 days of end of chemotherapy and assessment of patients' emotional well-being by second office visit. Three tiers of achievement were set for each goal. A formula combining VC goals into year-end payout was driven by three levels of percent base salary: 8%, 12%, and 24%, with probability of achievement of each goal of 90%, 50%, and 10%, respectively. Practice leadership was educated about QOPI acceptance in the oncology community. RESULTS: The division participated in QOPI during spring and fall 2012. With systems-based improvements, 40.54% of medical records audited had treatment summaries, resulting in achievement of tier III compensation. Documentation of emotional well-being increased, yielding 63% of patient cases compliant; however, the national benchmark concurrently improved, making this insufficient to achieve tier I. CONCLUSION: QOPI metrics can be used as a quality incentive for oncologists in a VC plan. Non-oncologists can appreciate the strength of QOPI as a quality tool. The combination of a QOPI program through ASCO and use of various QOPI metrics can drive continuous improvement in an oncology group.

Pregnancy offers new insights into mechanisms of breast cancer risk and resistance.

Pregnancy induces long-lasting changes in gene expression that are associated with a reduction in breast cancer risk. Although several mechanisms have been proposed to mediate the reduction in breast cancer risk among parous women, recent studies focus attention on progenitor cells as major targets. The results suggest new biomarkers that may improve risk prediction and provide endpoints for assessment of clinical responses to prophylactic therapies.

Sorafenib or placebo with either gemcitabine or capecitabine in patients with HER-2-negative advanced breast cancer that progressed during or after bevacizumab.

PURPOSE: We assessed adding the multikinase inhibitor sorafenib to gemcitabine or capecitabine in patients with advanced breast cancer whose disease progressed during/after bevacizumab. EXPERIMENTAL DESIGN: This double-blind, randomized, placebo-controlled phase IIb study (ClinicalTrials.gov NCT00493636) enrolled patients with locally advanced or metastatic human epidermal growth factor receptor 2 (HER2)-negative breast cancer and prior bevacizumab treatment. Patients were randomized to chemotherapy with sorafenib (400 mg, twice daily) or matching placebo. Initially, chemotherapy was gemcitabine (1,000 mg/m(2) i.v., days 1, 8/21), but later, capecitabine (1,000 mg/m(2) orally twice daily, days 1-14/21) was allowed as an alternative. The primary endpoint was progression-free survival (PFS). RESULTS: One hundred and sixty patients were randomized. More patients received gemcitabine (82.5%) than capecitabine (17.5%). Sorafenib plus gemcitabine/capecitabine was associated with a statistically significant prolongation in PFS versus placebo plus gemcitabine/capecitabine [3.4 vs. 2.7 months; HR = 0.65; 95% confidence interval (CI): 0.45-0.95; P = 0.02], time to progression was increased (median, 3.6 vs. 2.7 months; HR = 0.64; 95% CI: 0.44-0.93; P = 0.02), and overall response rate was 19.8% versus 12.7% (P = 0.23). Median survival was 13.4 versus 11.4 months for sorafenib versus placebo (HR = 1.01; 95% CI: 0.71-1.44; P = 0.95). Addition of sorafenib versus placebo increased grade 3/4 hand-foot skin reaction (39% vs. 5%), stomatitis (10% vs. 0%), fatigue (18% vs. 9%), and dose reductions that were more frequent (51.9% vs. 7.8%). CONCLUSION: The addition of sorafenib to gemcitabine/capecitabine provided a clinically small but statistically significant PFS benefit in HER2-negative advanced breast cancer patients whose disease progressed during/after bevacizumab. Combination treatment was associated with manageable toxicities but frequently required dose reductions.

Spectrum of breast disease encountered in HIV-positive patients at a community teaching hospital.

INTRODUCTION: HIV infection directly and indirectly affects breast tissue. This study describes the spectrum of HIV-related breast disease encountered at a community teaching hospital. METHODS: A 9 year retrospective review was performed of HIV-positive patients with a breast-related diagnosis seen at our institution. Patient demographics, HIV status, comorbid disease, medications, clinical findings, diagnostic procedure, pathology, treatment and outcome were recorded. RESULTS: A total of 46 individuals were included with a median age of 47 years (range 24-64 years) and male:female ratio of 1:3 (12 men and 34 women). Mean duration of HIV infection was 7 years during which time 46% of patients had an AIDS defining illness. Median CD4 cell count was 437 cells/mm(3) (range 2 to ≥500 cells/mm(3)) at the time of the breast diagnosis. Breast disease identified included benign conditions (59% total: 92% for men, 47% for women), infection (17% total: 8% for men, 21% for women), cancer (22% total: 0% for men, 29% for women), and atypia (2% total: 0% for men, 3% for women). Patients with a breast infection had a lower median CD4 cell count than those with breast cancer or benign conditions. Gynecomastia was detected in seven out of 12 (58%) men. In these men, antiretroviral therapy (ART) of all drug classes was associated with gynecomastia. Breast cancer occurred only in women and included patients with invasive ductal carcinoma (n = 7), ductal carcinoma in situ (n = 2), and liposarcoma diagnosed in one individual. Specific risk factors for breast cancer in this setting were not identified. Five (11%) patients died, only one from breast disease during the study period. CONCLUSION: These data indicate that increased longevity in patients with chronic HIV infection may be associated with the occurrence of breast conditions in both men and women. A broad spectrum of breast disease should be anticipated in HIV-infected persons living longer with effective ART.

Chronic diarrhea associated with persistent norovirus excretion in patients with chronic lymphocytic leukemia: report of two cases.

BACKGROUND: Chronic diarrhea in patients treated with immunosuppressive agents or suffering from immunosuppressive disease can represent a diagnostic and therapeutic challenge to the clinician. Norovirus infection, a major cause of acute epidemic diarrhea, has been described as a cause of chronic diarrhea in patients who are immunosuppressed, including transplant recipients and the very young. CASE PRESENTATIONS: We describe two patients, a 64 year-old man and a 59 year-old woman, both suffering from chronic lymphocytic leukemia and hypogammaglobulinemia, who developed chronic diarrhea resistant to therapy. In both cases, after months of symptoms, persistent norovirus infection--documented by repeatedly-positive high-sensitivity stool enzyme immunoassay--was found to be the cause. Both patients died with active diarrheal symptoms. CONCLUSIONS: We describe the first cases of advanced chronic lymphocytic leukemia to suffer from chronic symptomatic norovirus infection. Clinicians caring for such patients, particularly those with concomitant hypogammaglobulinema, who have chronic unexplained diarrhea, should consider norovirus infection in the differential diagnosis.

Does therapeutic touch ease the discomfort or distress of patients undergoing stereotactic core breast biopsy? A randomized clinical trial.

OBJECTIVE: To determine whether therapeutic touch administered at the time of stereotactic core biopsy of suspicious breast lesions results in a reduction in anxiety and pain. DESIGN: Randomized, patient-blinded, controlled trial of either Krieger-Kunz therapeutic touch administered by a trained practitioner or a sham intervention mimicking therapeutic touch delivered during core biopsy. SETTING: Stereotactic breast biopsy unit of a comprehensive breast center. PATIENTS: Women with mammographically detected, nonpalpable breast lesions requiring biopsy. OUTCOME MEASURES: Changes in pain and anxiety measured by visual analog scales immediately before and after stereotactic core biopsy. RESULTS: A total of 82 patients were accrued: 42 received actual therapeutic touch and 40 sham therapeutic touch. No significant differences were found between the arms for age, ethnicity, educational background, or other demographic data. The sham arm had a preponderance of left breast biopsies (48% vs 58%; P = 0.07) and received a slightly higher volume of epinephrine-containing local anesthetic (6.5 +/- 6.1 vs 4.5 +/- 4.5 mL; P = 0.09). Therapeutic touch patients were more likely to have an upper breast lesion location (57% vs 53%; P = 0.022). No significant differences between the arms were seen regarding postbiopsy pain (P = 0.95), anxiety (P = 0.66), fearfulness, or physiological parameters. Similarly, no differences were seen between the arms when change in parameters from prebiopsy to postbiopsy was considered for any of the psychological or physiological variables measured. These findings persisted when confounding variables were controlled for. CONCLUSIONS: Women undergoing stereotactic core breast biopsy received no significant benefit from therapeutic touch administered during the procedure. Therapeutic touch cannot be routinely recommended for patients in this setting.

Longitudinal patterns of weight gain after breast cancer diagnosis: observations beyond the first year.

Many, but not all patients experience weight gain 1 year after a breast cancer diagnosis; clearly defined, clinically relevant groups at risk of weight gain have yet to be described. We set out to determine the factors associated with weight gain over time in patients with invasive breast cancer during a period of predominantly anthracycline-based adjuvant chemotherapy and to identify groups with differing weight gain risks. Breast cancer patients (stage I-IIIB) were identified in a retrospective chart review. Evaluated parameters included weight at diagnosis and 1, 2, and 3 years later, height, body mass index (BMI), age, menopausal and change in menopausal status, as well as therapy and pathologic stage. Regression models identified significant independent predictors of weight change. Recursive partitioning analysis (RPA) was employed to divide the dataset into relevant and significant groups. In 185 identified patients, regression models and RPA demonstrated that weight gain at 1 year was associated with younger age, adjuvant chemotherapy, and lower BMI. Weight gain at 2 years (n = 176) was greater than at year 1, and in addition to weight gain at year 1, was associated with younger age and adjuvant chemotherapy in regression analysis; RPA found that anthracycline therapy, age, and BMI were important. Weights at 3 years were similar to those seen at 2 years. Early-stage breast cancer patients treated with chemotherapy continue to gain weight 2 years after diagnosis, and this weight gain appears to be persistent at year 3. Observation beyond 1 year is needed to adequately evaluate weight gain in early-stage breast cancer patients, particularly for those receiving contemporary adjuvant chemotherapy.