Positive Nipple Margins in Nipple-Sparing Mastectomy: Management of Nipples Containing Cancer or Atypia.

BACKGROUND: Nipple-sparing mastectomy (NSM) is an oncologically safe approach for breast cancer treatment and prevention; however, there are little long-term data to guide management for patients whose nipple margins contain tumor or atypia. METHODS: NSM patients with tumor or atypia in their nipple margin were identified from a prospectively maintained, single-institution database of consecutive NSMs. Patient and tumor characteristics, treatment, recurrence, and survival data were assessed. RESULTS: A total of 3158 NSMs were performed from June 2007 to August 2019. Nipple margins contained tumor in 117 (3.7%) NSMs and atypia only in 164 (5.2%) NSMs. Among 117 nipple margins that contained tumor, 34 (29%) margins contained invasive cancer, 80 (68%) contained ductal carcinoma in situ only, and 3 (3%) contained lymphatic vessel invasion only. Management included nipple-only excision in 67 (57%) breasts, nipple-areola complex excision in 35 (30%) breasts, and no excision in 15 (13%) breasts. Only 23 (24%) excised nipples contained residual tumor. At 67 months median follow-up, there were 2 (1.8%) recurrences in areolar or peri-areolar skin, both in patients with nipple-only excision. Among 164 nipple margins containing only atypia, 154 (94%) nipples were retained. At 60 months median follow-up, no patient with atypia alone had a nipple or areola recurrence. CONCLUSIONS: Nipple excision is effective management for nipple margins containing tumor. No intervention is required for nipple margins containing only atypia. Our results support broad eligibility for NSM with careful nipple margin assessment.

Choosing high-risk screening vs. surgery and the effect of treatment modality on anxiety and breast-specific sensuality in BRCA mutation carriers.

BACKGROUND: We have previously shown that breast cancer surgery affects breast specific sensuality, and that women who undergo mastectomy may have worse sexual function outcomes than those who undergo lumpectomy. It is less clear if patients who undergo prophylactic mastectomy are equally as affected as those with a cancer diagnosis. We sought to compare sexual function outcomes and their relationship to depression and anxiety between BRCA mutation carriers (mBRCA) with and without cancer in order to guide surgical counseling and improve survivorship outcomes. METHODS: A confidential, cross-sectional survey was distributed electronically to mBRCA at least 18 years of age. The survey included investigator-generated questions, the Female Sexual Function Index (FSFI), and the Hospital Anxiety and Depression Scale (HADS) surveys. Responses were analyzed in total and divided into two subgroups: those with and without breast cancer. RESULTS: Sixty-three mBRCA responded (37%) of 170 email addresses were identified, and 77% were postmenopausal. Although more than half of all mBRCA reported that the role of the breast in intimacy was important, most patients without cancer and all of those with cancer experienced an impressive decline in certain breast-specific sensuality parameters postoperatively. Among those without cancer, anxiety scores were not different between those choosing prophylactic mastectomy and high-risk screening (HRS). Sexual function as measured by the FSFI was negatively correlated with depression and anxiety in mBRCA. FSFI scores were not significantly different between those with and without cancer. However, the median FSFI of mBRCA with cancer, those undergoing HRS, and those who underwent prophylactic mastectomy indicated sexual dysfunction. CONCLUSIONS: As the availability of genetic testing increases, more women are found to harbor BRCA mutations and must choose between HRS and prophylactic surgery. Women with BRCA mutations, both with and without breast cancer, are susceptible to derangements in sexual function during the course of both screening or treatment, and this appears to be negatively correlated to depression and anxiety.

Sexual Dysfunction in Breast Cancer Survivors: Is it Surgical Modality or Adjuvant Therapy?

OBJECTIVES: Sexual dysfunction is common in breast cancer survivors. Our survey study aimed to delineate the relative associations between sexual dysfunction and breast cancer treatment including surgical modalities and adjuvant therapies. METHODS: Women in surveillance following breast cancer surgery were eligible for our survey incorporating the Female Sexual Function Index. Analysis involved multiple log-binomial regression to evaluate the association between sexual dysfunction (Female Sexual Function Index≤26.55) and treatment modality. RESULTS: Of the 600 completed surveys, the final eligible analytic sample included 278 sexually active respondents. Overall, 65%, 27%, and 8% underwent lumpectomy, mastectomy with reconstruction, and mastectomy alone, respectively. In total, 74.5% reported receipt of radiation; 47.8% chemotherapy; 27.3% tamoxifen, and 31.4% aromatase inhibitor (AI). No significant difference in prevalence of sexual dysfunction was observed by surgical modality, even when adjusted for adjuvant therapy. Chemotherapy or radiation was not associated with sexual dysfunction when adjusted for surgical modality. The prevalence of sexual dysfunction was 1.6 times higher for the AI group compared with the no endocrine therapy group (P=0.01), when adjusted for other treatment groups. CONCLUSIONS: Our study demonstrated that the highest rates of sexual dysfunction were among breast cancer survivors treated with AI. Neither surgical modality, chemotherapy, nor radiation was associated with sexual dysfunction. These data may guide clinicians in counseling sexually active breast cancer patients in treatment planning and survivorship.

Mycobacterium avium in Community and Household Water, Suburban Philadelphia, Pennsylvania, USA, 2010-2012.

Attention to environmental sources of Mycobacterium avium complex (MAC) infection is a vital component of disease prevention and control. We investigated MAC colonization of household plumbing in suburban Philadelphia, Pennsylvania, USA. We used variable-number tandem-repeat genotyping and whole-genome sequencing with core genome single-nucleotide variant analysis to compare M. avium from household plumbing biofilms with M. avium isolates from patient respiratory specimens. M. avium was recovered from 30 (81.1%) of 37 households, including 19 (90.5%) of 21 M. avium patient households. For 11 (52.4%) of 21 patients with M. avium disease, isolates recovered from their respiratory and household samples were of the same genotype. Within the same community, 18 (85.7%) of 21 M. avium respiratory isolates genotypically matched household plumbing isolates. Six predominant genotypes were recovered across multiple households and respiratory specimens. M. avium colonizing municipal water and household plumbing may be a substantial source of MAC pulmonary infection.

Intraoperative radiation therapy as part of planned monotherapy for early-stage breast cancer.

INTRODUCTION: Adjuvant whole breast radiation therapy has developed into the standard of care for patients following a lumpectomy for early-stage breast cancer. However, there is recent interest in intraoperative radiation therapy (IORT) to minimize toxicity while still improving local control beyond surgical resection and anti-estrogen therapy alone. MATERIALS AND METHODS: All patients were evaluated pre-operatively in a multidisciplinary clinic setting at a community hospital for suitability for breast conservation therapy. A total of 109 patients were reviewed receiving 110 IORT treatments. Patients were followed with clinical breast examinations and mammography as clinically indicated. RESULTS: At a median follow-up of 29.9 months, 2/110 (1.8%) patients experienced a local failure. One patient (0.9%) experienced a regional failure. Local control, disease-free survival and overall survival at 3 years were 98.9% (95%CI 92.2-99.8), 97.2% (95%CI 88.9-99.3), and 96.0% (95%CI 84.9-99.0), respectively. Five-year local control, disease-free survival, and overall survival rates were 96.3% (95%CI 84.7-99.2), 94.6% (95%CI 83.2-98.3), and 92.5% (95%CI 80.4-97.3), respectively. Patient self-reported cosmetic outcome was available for 51 patients, with all patients reporting being either very pleased, pleased, or satisfied with their cosmetic outcome, and no patients reported being dissatisfied or worse. CONCLUSIONS: The results of our series suggest the feasibility of utilizing IORT in a community-based cancer center with a high degree of local control, and patient satisfaction with regard to cosmesis. While the results of this series suggest that IORT may be a promising modality, longer follow-up is warranted to better understand exactly which clinicopathological features can predict long-term locoregional disease control.

Influential Forces in Breast Cancer Surgical Decision Making and the Impact on Body Image and Sexual Function.

BACKGROUND: Shared decision making with one's partner and body image satisfaction may affect surgical choices of breast cancer patients. This study analyzed whether partner opinion was associated with choice of operation and whether comfort level with one's partner was altered postoperatively. METHODS: A prospective anonymous survey was administered to breast cancer patients who underwent breast surgery between 2000 and 2014. Categorical variables were compared by χ (2) or Fisher's exact test. RESULTS: Women who elected to undergo mastectomy with reconstruction (MR) placed greater emphasis on their own decision making than on input from their partner, surgeon, or others (56.5 vs. 8.3 vs. 23.2 vs. 12, respectively), whereas those who chose lumpectomy (L) placed similar weight on surgeon input and self-input (44.2 vs. 42.7 %). Only 7.5 % of all patients identified their partner as the greatest influence on their surgical choice. Preoperatively, the L group was the most comfortable with their partner seeing their chest (91.9 % L vs. 83.9 % MR vs. 75.9 % mastectomy alone (M); p = 0.01), and postoperatively, the comfort levels for all were remarkably decreased. Furthermore, if a patient was a candidate for L but chose MR, the role her chest played in intimacy dropped more compared with those who chose L (83.8 % L vs. 91.7 % MR; p = 0.3 preoperatively to 65.1 % L vs. 42.9 % MR; p = 0.01 postoperatively). CONCLUSIONS: When making surgical decisions, most patients indicate that they value their own opinion over that of others. Mastectomy, regardless of reconstruction, leads to a significant reduction in comfort with one's partner postoperatively compared with lumpectomy. This information may be helpful in counseling couples at the time of consultation for breast cancer treatment.

Methylobacterium spp. as an indicator for the presence or absence of Mycobacterium spp.

OBJECTIVE/BACKGROUND: A published survey of bacteria in showerhead biofilm samples revealed that Methylobacterium spp. and Mycobacterium spp. seldom coexisted in biofilms. METHODS: To confirm that information, biofilm samples were collected from household plumbing of Mycobacterium avium patients and Methylobacterium spp. and M. avium numbers were measured by direct colony counts. RESULTS: The results demonstrated that if Methylobacterium spp. were present, Mycobacterium spp. were absent, and the opposite. CONCLUSION: The data demonstrate that microbial populations in biofilms can influence the presence or absence of opportunistic premise plumbing pathogens and, thereby, increase the range of strategies to reduce exposure to waterborne pathogens. Finally, by assessing for the visual presence of methylobacteria as pink pigmentation on showers and shower curtains, homeowners and managers of hospitals and other buildings can quickly determine whether a premise plumbing biofilm sample has mycobacteria with a high degree of assurance.

Variable-Number Tandem-Repeat Analysis of Respiratory and Household Water Biofilm Isolates of "Mycobacterium avium subsp. hominissuis" with Establishment of a PCR Database.

"Mycobacterium aviumsubsp.hominissuis" is an important cause of pulmonary disease. It is acquired from environmental sources, but there is no methodology for large population studies. We evaluated the potential of variable-number tandem-repeat (VNTR) analysis. Clinical and household biofilmM. aviumisolates underwent molecular identification. Testing for IS901was done to separateM. aviumsubsp.aviumfromM. aviumsubsp.hominissuis VNTR types were defined using VNTR loci, and subtyping was performed using 3'hsp65and internal transcribed spacer (ITS) sequencing. Forty-nine VNTR types and eight subtypes ofM. aviumsubsp.hominissuis(IS901negative) were identified among 416 isolates ofM. aviumfrom 121 patients and 80 biofilm sites. Of those types, 67% were found only among patient isolates, 11% only among household water isolates, and 23% among both. Of 13 VNTR types that included ≥4 patients, the majority (61.5%) represented geographic clustering (same city). Most VNTR types with multiple patients belonged to the same 3'hsp65sequence code (sequevar). A total of 44 isolates belonging to fourM. aviumsubsp.hominissuisVNTR types (8%), including three with the rare Mav-F ITS sequence and 0/8 subspecies, produced amplicons with IS901PCR primers. By sequencing, all 44 amplicons were not IS901but ISMav6, which was recently observed in Japan but had not been previously described among U.S. isolates. VNTR analysis ofM. aviumsubsp.hominissuisisolates is easier and faster than pulsed-field gel electrophoresis. Seven VNTR loci separated 417 isolates into 49 types. No isolates ofM. aviumsubsp.aviumwere identified. The distributions of the VNTR copy numbers, the allelic diversity, and the low prevalence of ISMav6 differed from the findings for respiratory isolates reported from Japan.

Normal estrogen, but low dehydroepiandrosterone levels, in women with pulmonary Mycobacterium avium complex. A preliminary study.

RATIONALE: For unclear reasons, the phenotypical hosts for nontuberculous mycobacterial lung infection are often thin, elderly, white women without underlying lung disease. As these women are usually postmenopausal, we hypothesized that a state of relative hormone deficiency may predispose some women to pulmonary nontuberculous mycobacterial infection. OBJECTIVES: To conduct a prospective cross-sectional study to assess for alterations in systemic levels of sex hormones in patients with confirmed pulmonary Mycobacterium avium complex infection compared with healthy control subjects. METHODS: Female patients with pulmonary M. avium complex infection (n = 35) were recruited along with similar-aged control subjects (n = 27) without lung disease from the general population of our institution. Levels of dehydroepiandrosterone-sulfate (DHEA-S), estrone, and ultrasensitive estradiol were measured from sampled blood. MEASUREMENTS AND MAIN RESULTS: DHEA-S levels of patients with M. avium complex infection were significantly lower than control subjects (mean 33 µg/dl vs. 59 µg/dl, P = 0.001). No significant difference was found in the levels of estrone (mean, 27 pg/ml vs. 28 pg/ml, P = 0.665) or ultrasensitive estradiol (mean, 9 pg/ml vs. 9 pg/ml, P = 0.364). Patients with M. avium complex had a lower body mass index (BMI) than control subjects (mean, 22 vs. 26, P = 0.001). There was no association between levels of DHEA-S, estrone, or estradiol, and BMI or age. CONCLUSIONS: Women with M. avium complex infection had lower DHEA-S levels, but not lower estrogen levels, compared with control subjects. There was no relationship between BMI and hormone levels in the study population. Further study of these hormonal effects on immune function in nontuberculous mycobacterial infection is warranted.

Absence of Mycobacterium intracellulare and presence of Mycobacterium chimaera in household water and biofilm samples of patients in the United States with Mycobacterium avium complex respiratory disease.

Recent studies have shown that respiratory isolates from pulmonary disease patients and household water/biofilm isolates of Mycobacterium avium could be matched by DNA fingerprinting. To determine if this is true for Mycobacterium intracellulare, household water sources for 36 patients with Mycobacterium avium complex (MAC) lung disease were evaluated. MAC household water isolates from three published studies that included 37 additional MAC respiratory disease patients were also evaluated. Species identification was done initially using nonsequencing methods with confirmation by internal transcribed spacer (ITS) and/or partial 16S rRNA gene sequencing. M. intracellulare was identified by nonsequencing methods in 54 respiratory cultures and 41 household water/biofilm samples. By ITS sequencing, 49 (90.7%) respiratory isolates were M. intracellulare and 4 (7.4%) were Mycobacterium chimaera. In contrast, 30 (73%) household water samples were M. chimaera, 8 (20%) were other MAC X species (i.e., isolates positive with a MAC probe but negative with species-specific M. avium and M. intracellulare probes), and 3 (7%) were M. avium; none were M. intracellulare. In comparison, M. avium was recovered from 141 water/biofilm samples. These results indicate that M. intracellulare lung disease in the United States is acquired from environmental sources other than household water. Nonsequencing methods for identification of nontuberculous mycobacteria (including those of the MAC) might fail to distinguish closely related species (such as M. intracellulare and M. chimaera). This is the first report of M. chimaera recovery from household water. The study underscores the importance of taxonomy and distinguishing the many species and subspecies of the MAC.

Association between pulmonary mycobacterium avium complex infection and lung cancer.

INTRODUCTION: Patients with lung cancer are sometimes found to have respiratory cultures growing Mycobacterium avium complex (MAC). This study describes the clinical, pathologic, and radiographic -characteristics of individuals who harbor concomitant lung cancer and MAC. METHODS: Retrospective analysis of patients with positive respiratory cultures for MAC (370 men, 475 women) and with newly diagnosed lung cancer (792 men, 840 women) from 1995 to 2010. RESULTS: Of the patients with respiratory cultures growing MAC, 8.6% of men and 6.3% of women had lung cancer. Twenty-five percent of patients with lung cancer and 3% with nonbronchiectatic benign lung disease grew MAC from their respiratory cultures. Significantly fewer women with both MAC and lung cancer were smokers than the control group of women with lung cancer and negative MAC cultures (68% versus 89%, p < 0.01). Squamous cell carcinoma occurred in 40% of women in the MAC/lung cancer group versus 28% of women in the lung cancer control group. Peripherally located squamous cell carcinomas were found in 71% of the MAC/lung cancer group versus 40% of the lung cancer control group (p = 0.01) CONCLUSIONS: The percentage of smokers among women with both MAC and lung cancer was lower than among the lung cancer control group who did not grow MAC. The presence of MAC in respiratory cultures of lung cancer patients was particularly associated with squamous cell carcinomas located in the periphery of the lung. Because MAC typically affects distal airways, this possible association between MAC infection and lung cancer warrants further study.