Reasons for risk-reducing mastectomy versus MRI-screening in a cohort of women at high hereditary risk of breast cancer

Objective

To determine the reasons that motivate women in a cohort of women under intensive surveillance for breast cancer to undergo risk-reducing mastectomy (RRM).

Patients and methods

Women with a BRCA1 or BRCA2 mutation who were enrolled in an MRI-based breast screening study were eligible to participate in this survey. A self-administered questionnaire was given to women who did, and who did not terminate annual MRI-based surveillance in order to undergo RRM. The questionnaire included information on family history, risk perception and satisfaction with screening. In addition, women were asked to provide the principal reason for their choice of having preventive surgery or not, and were asked about their satisfaction with this choice.

Results

246 women without breast cancer participated in the study. Of these, 39 women (16%) elected to have RRM at some point after initiating screening. Although women who had a mother or sister with breast cancer were more likely to opt for RRM than were women with no affected first-degree relative (21% versus 10%) this did not reach statistical significance. Women who perceived their breast cancer risk to be greater than 50% were more likely to opt for RRM than were women who estimated their risk to be less than 50% (19% versus 6%). Fear of cancer was the most common reason cited for choosing to have RRM (38% of respondents) followed by having had a previous cancer, (25%), then concern over their children (16%).

Conclusion

Among women with a BRCA mutation who are enrolled in an MRI-based screening program, a high perception of personal breast cancer risk and a history of breast cancer in a first-degree relative are predictors of the decision to have RRM.     

Sexuality and quality of life in women with a prior diagnosis of breast cancer after risk-reducing salpingo-oophorectomy

ObjectivesTo investigate the prevalence of sexual dysfunction in women with a history of breast cancer following risk-reducing salpingo-oophorectomy (RRSO). A secondary objective was to examine the effect of a prior diagnosis of breast cancer, and other factors, on sexuality and quality of life (QoL) outcomes.Study designCross-sectional study of 119 women who underwent RRSO between 2009 and 2014.Main outcome measuresData were collected via a questionnaire comprising demographic information and validated measures of sexual function, sexual distress, relationship satisfaction, body image, psychological stress, menopause symptoms and general quality of life.ResultsSixty out of 119 participants who underwent RRSO had a history of breast cancer. Eighty percent of women with breast cancer had female sexual dysfunction (FSD) and 82% had hypoactive sexual desire disorder (HSDD) after RRSO. Bilateral mastectomy was associated with higher rates of HSDD (p = 0.028) and higher body image self-consciousness (BISC) during sexual activity (p = 0.011). Breast reconstruction was associated with higher relationship satisfaction (RAS) scores (p = 0.004). Compared to Tamoxifen, aromatase inhibitors (AI) were significantly associated with reduced lubrication (p = 0.041), arousal (p = 0.004), orgasm (p = 0.002) and greater dyspareunia (p = 0.027). Prior diagnosis of breast cancer was not associated with the prevalence of FSD (p = 0.532).ConclusionsHigh rates of FSD and HSDD occur in women with breast cancer following RRSO. Low relationship satisfaction, bodily pain, bilateral mastectomy and the use of aromatase inhibitors were associated with poorer sexual function. Women had similar sexual outcomes and QoL after RRSO, regardless of breast cancer history.     

Patient and provider factors associated with the noninitiation of tamoxifen for young women at high‐risk for the development of breast cancer

We sought to identify factors associated with disparities in tamoxifen utilization among young patients at high‐risk for developing breast cancer. We identified 67 premenopausal, high‐risk women age 35‐45, without surgical prophylaxis, who did not initiate tamoxifen. Factors associated with noninitiation were examined. About 37% of patients had no documented provider‐based discussion regarding initiation. Type of high‐risk diagnosis was the only factor associated with a provider‐based discussion (P = .03). For patients offered tamoxifen, primary reasons for noninitiation were perceived minimal benefit (66.7%), fertility concerns (16.7%), and concerns about side effects (7.1%). Implementation of comprehensive educational strategies regarding the benefits of tamoxifen should be facilitated to improve initiation among young high‐risk patients.     

A novel patient decision aid for aftercare in breast cancer patients: A promising tool to reduce costs by individualizing aftercare

ObjectiveA patient decision aid (PtDA), was developed to support breast cancer patients making choices about their aftercare. The aim of this pilot was to test the effects of the PtDA on Shared Decision Making (SDM), Decision Evaluation (DES) in patients, consultation time, choice of aftercare and hospital costs.MethodsA prospective before-and-after study including a control (no PtDA-usage) and experimental group (PtDA-usage during consultation) was conducted in six hospitals. Patients were offered a choice between intensive (face-to-face consultations) and less intensive (telephonic or on demand consultations) aftercare. All patients filled out three validated questionnaires (baseline (T0), directly after the consultation (T1), three months later (T2)), assessing demographics (T0), SDM(T1) and DES (T1, T2). Hospital costs and choice of aftercare were assessed from the patients' files (T2). Effect sizes ( ɳ_p²: 0.01 = small; 0.06 = medium; 0.14 = large; φ: 0.1 = small, 0.3 = medium, 0.5 = large) and p-values were calculated using both univariate and multivariate GLMs, a repeated measures GLM and chi-square-tests.ResultsA small improvement in SDM ( ɳ_p² = 0.02) and an effect ( ɳ_p² = 0.10) on DES was found in the experimental group. Significantly more PtDA-users (51% vs. 29%, φ = 0.22) chose less intensive aftercare, leading to a small reduction of hospital costs (122 vs. 92 Euro, ɳ_p² = 0.01), and a large increase in average consultation time (12.5 min; ɳ_p² = 0.29).ConclusionThis pilot study showed promising effects of the PtDA on SDM and hospital costs. The PtDA can be developed further to potentially reduce the increased consultation time.     

基层医院成人急性肠梗阻急诊手术时机的决策

[摘要]目的探讨成人急性肠梗阻急诊手术时机的决策。方法我院普外科2006年9月～2012年12月共收治急性肠梗阻病人158例,其中105例（66．5％）行急诊手术,对其临床效果进行回顾性总结。结果本组105例病人均经急诊剖腹探查术,手术距发病时间平均28h,术后发生肠瘘3例,2例保守治疗痊愈,1例死亡。结论及时的早期诊断及准确的手术决策是改善本病预后,降低并发症及病死率的关键。     

保留乳头乳晕复合体的乳腺癌改良根治术预后的相关因素分析

目的探究影响保留乳头乳晕复合体(NAC)的乳腺癌改良根治术(NSM)预后的相关因素。 方法回顾性分析2011年1月至2014年12月84例早期原发性乳腺癌并接受NAC的NSM患者临床病理资料。使用统计软件SPSS 20.0进行数据分析,采用K-M生存曲线评估术后无病生存(DFS)及总生存(OS),采用单因素分析和Cox多因素分析影响NSM术后患者DFS和OPS的影响因素。P<0.05差异有统计学意义。 结果术后局部复发8例,远处转移6例,术后5年DFS为83.3%,OS为91.7%。多因素分析显示,肿瘤最大径、肿瘤距乳头乳晕距离(TND)、腋窝淋巴结状态、组织学类型及Her-2阳性是影响DFS的独立危险因素(P<0.05);而腋窝淋巴结状态是影响术后OS的独立危险因素(P<0.05)。 结论肿瘤最大径、TND、腋窝淋巴结状态、组织学类型及Her-2阳性是DFS的独立危险因素,腋窝淋巴结状态是OS的独立危险因素;腋窝淋巴结情况同时影响患者术后DFS和OS,术前系统、精准地评估并妥善处理特殊腋窝淋巴结可提高乳腺癌患者预后。     

Factors associated with decision to pursue mastectomy and breast reconstruction for treatment of ductal carcinoma in situ of the breast

Background

Factors influencing the treatment of ductal carcinoma in situ with mastectomy and reconstruction are poorly understood.

Methods

A retrospective cohort study of 196 patients presenting to one institution was performed.

Results

Forty-seven patients (24.0%) were treated with mastectomy, while 149 (76.0%) underwent breast-conserving surgery. Of the mastectomy patients, 28 (59.6%) elected for reconstruction. On bivariate analysis, patients who opted for mastectomy were younger than those treated with breast-conserving surgery (median age, 51.8 vs 56.5 years; P = .017) and had higher grade tumors (50.0% vs 34.6% grade 3, P = .009). Among patients treated with mastectomy, those who opted for reconstruction were younger than those forgoing reconstruction (49.4 vs 56.9 years, P = .024). Race, ductal carcinoma in situ tumor size, and histologic subtype were not associated with the decision to pursue mastectomy or reconstruction (P > .05 for all).

Conclusions

In patients with ductal carcinoma in situ, the decision to pursue mastectomy and reconstruction appears to be driven by younger patient age and higher tumor grade.     

Terminal Duct Lobular Units are Scarce in the Nipple: Implications for Prophylactic Nipple-Sparing Mastectomy

Background The use of nipple-sparing mastectomy (NSM) for both breast cancer treatment and risk reduction is increasing. There is no randomized data comparing nipple-sparing mastectomy with standard mastectomy techniques. There is evidence to suggest that ductal and lobular breast cancer arises in the terminal duct/lobular unit (TDLU). This study was undertaken to determine whether TDLUs exist in the nipple and if so, to what extent. Methods At the time of mastectomy the nipple papilla was excised and submitted for separate pathological examination. The presence or absence of TDLUs was noted. Results Thirty-two nipples were studied in 22 patients. There were no TDLUs in 29 specimens. Three of 32 nipple specimens were found to contain TDLUs. The three nipples contain one, two, and three TDLUs respectively. All TDLUs were found at the base of the nipple, with none located near the tip. Conclusions The infrequent occurrence of TDLUs in the nipple papilla supports the use of NSM for risk reduction surgery, including for those women with BRCA1/2 mutations.     

Hospital organizational factors affect the use of immediate breast reconstruction after mastectomy for breast cancer in the Netherlands

ObjectivesSignificant hospital variation in the use of immediate breast reconstruction (IBR) after mastectomy exists in the Netherlands. Aims of this study were to identify hospital organizational factors affecting the use of IBR after mastectomy for ductal carcinoma in situ (DCIS) or invasive breast cancer (BC) and to analyze whether these factors explain the variation.Materials and methodsPatients with DCIS or primary invasive BC treated with mastectomy between 2011 and 2013 were selected from the national NABON Breast Cancer Audit. Hospital and organizational factors were collected with an online web-based survey. Regression analyses were performed to determine whether these factors accounted for the hospital variation.ResultsIn total, 78% (n = 72) of all Dutch hospitals participated in the survey. In these hospitals 16,471 female patients underwent a mastectomy for DCIS (n = 1,980) or invasive BC (n = 14,491) between 2011 and 2014. IBR was performed in 41% of patients with DCIS (hospital range 0–80%) and in 17% of patients with invasive BC (hospital range 0–62%). Hospital type, number of plastic surgeons available and attendance of a plastic surgeon at the MDT meeting increased IBR rates. For invasive BC, higher percentage of mastectomies and more weekly MDT meetings also significantly increased IBR rates. Adjusted data demonstrated decreased IBR rates for DCIS (average 35%, hospital range 0–49%) and invasive BC (average 15%, hospital range 0–18%).ConclusionHospital organizational factors affect the use of IBR in the Netherlands. Although only partly explaining hospital variation, optimization of these factors could lead to less variation in IBR rates.     

Germline BRCA mutation does not prevent response to taxane-based therapy for the treatment of castration-resistant prostate cancer

Study Type – Prognosis (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? In the preclinical setting BRCA mutations appear to modulate response to chemotherapy, increasing sensitivity to platinums and increasing resistance to taxanes. Clinical data supports a greater platinum sensitivity among BRCA mutation carriers. This study suggests that BRCA mutation carriers may also respond to taxanes.

OBJECTIVE

? To investigate the relationship between BRCA mutation status and response to taxane‐based chemotherapy, since BRCA mutation carriers with prostate cancer appear to have worse survival than non‐carriers and docetaxel improves survival in patients with castration‐resistant prostate cancer.

PATIENTS AND METHODS

? We determined BRCA mutation prevalence in 158 Ashkenazi Jewish (AJ) men with castration‐resistant prostate cancer. Clinical data were collected as part of an institutional prostate cancer research database and through additional medical record review. ? Clinical records and DNA samples were linked through a unique identifier, anonymizing the samples before genetic testing for the AJ BRCA1/2 founder mutations. ? Response to taxane‐based therapy was defined by the prostate‐specific antigen nadir within 12 weeks of therapy.

RESULTS

? In all, 88 men received taxane‐based treatment, seven of whom were BRCA carriers (three BRCA1, four BRCA2; 8%). Initial response to taxane was available for all seven BRCA carriers and for 69 non‐carriers. ? Overall, 71% (54/76) of patients responded to treatment, with no significant difference between carriers (57%) and non‐carriers (72%) (absolute difference 15%; 95% confidence interval –23% to 53%; P= 0.4). ? Among patients with an initial response, the median change in prostate‐specific antigen was similar for BRCA carriers (?63%, interquartile range ?71% to ?57%) and non‐carriers (?60%, interquartile range ?78% to ?35%) (P= 0.6). ? At last follow‐up, all seven BRCA carriers and 49 non‐carriers had died from prostate cancer. One BRCA2 carrier treated with docetaxel plus platinum survived 37 months.

CONCLUSION

? In this small, hypothesis‐generating study approximately half of BRCA carriers had a prostate‐specific antigen response to taxane‐based chemotherapy, suggesting that it is an active therapy in these individuals.     

A cost-utility analysis comparing large volume displacement oncoplastic surgery to mastectomy with single stage implant reconstruction in the treatment of breast cancer

BackgroundFor larger cancers in moderate to large breast sized women, breast surgical cancer treatment may include large volume displacement oncoplastic surgery (LVOS) or mastectomy with single stage implant reconstruction (SSIR). Often in the case of LVOS, reduction mammaplasty designs are used in the oncoplastic reconstructions with a contralateral symmetry operation. The goal of this study was to investigate the cost-utility between LVOS versus SSIR to determine which approach is cost-effective in the treatment of breast cancer.MethodsA review of the literature was performed to determine baseline values and ranges. An average national Medicare payment rates using DRG and CPT codes were used for cost assessment. After constructing a decision tree, an incremental cost-utility ratio (ICUR) was calculated comparing the difference for both surgical options in costs by the difference in clinical-effectiveness. To validate our results, we performed one-way sensitivity analyses in addition to a Monte-Carlo analysis.ResultsAn ICUR of $546.81/QALY favoring LVOS was calculated based off of its clinical-effectiveness gain of 7.67 QALY at an additional cost of $4194. One-way sensitivity analyses underscored the degree by which LVOS was cost-effective. For example, LVOS became cost-ineffective when a successful LVOS cost more than $50,000. Similarly, probabilistic sensitivity analysis using Monte-Carlo simulation showed that even with varying multiple variables at once, results tended to favor our conclusion supporting the cost-effectiveness of LVOS.ConclusionsFor the appropriate patients with moderate to large sized breasts with breast cancer, large volume displacement oncoplastic surgery is cost-effective compared to mastectomy with single staged implant reconstruction.     

Germline mutation screening of the Saethre-Chotzen-associated genes TWIST1 and FGFR3 in families with BRCA1/2-negative breast cancer

Saethre-Chotzen syndrome is one of the most common craniosynostosis syndromes. It is an autosomal dominantly inherited disorder with variable expression that is caused by germline mutations in the TWIST1 gene or more rarely in the FGFR2 or FGFR3 genes. We have previously reported that patients with Saethre-Chotzen syndrome have an increased risk of developing breast cancer. Here we have analysed a cohort of 26 women with BRCA1/2-negative hereditary breast cancer to study whether a proportion of these families might have mutations in Saethre-Chotzen-associated genes. DNA sequence analysis of TWIST1 showed no pathogenic mutations in the coding sequence in any of the 26 patients. MLPA (multiplex ligation-dependent probe amplification)-analysis also showed no alterations in copy numbers in any of the craniofacial disorder genes MSX2, ALX4, RUNX2, EFNB1, TWIST1, FGFR1, FGFR2,FGFR3, or FGFR4. Taken together, our findings indicate that mutations in Saethre-Chotzen-associated genes are uncommon or absent in BRCA1/2-negative patients with hereditary breast cancer.     

A case of gastric cancer metastasis to the breast in a female with BRCA2 germline mutation and literature review

Introduction: Gastric cancer is a deadly disease. Common sites of distant metastasis of gastric cancer are the peritoneum, liver, lymph nodes, and lung. The breast is a rare site of metastasis in gastric cancer which occurs in males dominantly.

Patients and methods: Here, we report the first case of metastatic gastric cancer to the breast in a patient with the breast cancer 2 (BRCA2) germline mutation. A 34-year-old female was admitted to the hospital with dyspepsia and a palpable mass in the left breast. Gastric cancer was confirmed to be signet ring cell adenocarcinoma. The breast mass exhibited histological properties consistent with gastric cancer. Immunohistochemistry results showed the breast tumor was CDX-2 and CK20-positive, but ER-, CK7-, and GATA3-negative. The BRCA1 gene had a wild-type sequence, but a heterozygous variant was discovered in BRCA2 in exon 10 (c.1744A?>?C, p.T582P); the significance of this variant is unknown.

Results: The patient received palliative XELOX (capecitabine?+?oxaliplatin) with radiation therapy to the stomach. The breast tumor resolved completely, but the overall response was partial.

Conclusion: Gastric cancer metastasis to the breast is rare, but should be considered in young female patients with signet ring cell type gastric cancer.     

Breast cancer in women at high risk: The role of rapid genetic testing for BRCA1 and -2 mutations and the consequences for treatment strategies

Specific clinical questions rise when patients, who are diagnosed with breast cancer, are at risk of carrying a mutation in BRCA1 and -2 gene due to a strong family history or young age at diagnosis. These questions concern topics such as 1. Timing of genetic counseling and testing, 2. Choices to be made for BRCA1 or -2 mutation carriers in local treatment, contralateral treatment, (neo)adjuvant systemic therapy, and 3. The psychological effects of rapid testing. The knowledge of the genetic status might have several advantages for the patient in treatment planning, such as the choice whether or not to undergo mastectomy and/or prophylactic contralateral mastectomy. The increased risk of developing a second breast cancer in the ipsilateral breast in mutation carriers, is only slightly higher after primary cancer treatment, than in the general population. Prophylactic contralateral mastectomy provides a substantial reduction of contralateral breast cancer, although only a small breast cancer specific survival benefit. Patients should be enrolled in clinical trials to investigate (neo)-adjuvant drug regimens, that based on preclinical and early clinical evidence might be targeting the homologous recombination defect, such as platinum compounds and PARP inhibitors. If rapid testing is performed, the patient can make a well-balanced decision. Although rapid genetic counseling and testing might cause some distress, most women reported this approach to be worthwhile. In this review the literature regarding these topics is evaluated. Answers and suggestions, useful in clinical practice are discussed.     

The contribution of inherited factors to the clinicopathological features and behavior of breast cancer

This review is focused on genetic factors that may influence the development and/or appearance of breast cancer metastases. Over the last decade there have been significant advances in the understanding of genetic predisposition to breast cancer. The first breast cancer predisposing gene to be identified was TP53, and this was followed over the next 5 years by two more genes, BRCA1 and BRCA2, which from a population perspective are much more important than TP53. Other rarer genes have subsequently been identified, but the role of more common, less penetrant genes in breast cancer susceptibility remains unknown. Recent work has shown that breast cancers occurring in women carrying germ-line BRCA1 mutations tend to have clinicopathological features that are usually associated with a poor prognosis, such as high grade, estrogen receptor negative status and somatic TP53 mutations. On the other hand, they are usually ERBB2 negative. Whether or not such tumors are more or less likely to metastasize, and hence be associated with a poor outcome, is currently uncertain and has been the subject of much debate. Here, we outline some of the clinicopathological features of hereditary breast cancer, discuss the prognostic studies that have been performed, and introduce some possible new research directions.     

Prognostic factors for breast cancer patients with T1‐2 tumor and 1‐3 positive axillary nodes treated using total mastectomy without radiotherapy

Prospective randomized trials have demonstrated that postmastectomy radiotherapy (PMRT) improves not only locoregional recurrence‐free survival, but also overall survival for node‐positive breast cancer patients. Subset analyses in previous trials have shown that improvement of overall survival with PMRT is not always demonstrated for patients with 1‐3 positive nodes. Indications for PMRT are still marginal for patients with pathological invasion 5 cm in diameter and 1‐3 positive nodes. The aim of this study was to clarify poor prognostic factors for breast cancer patients with pathological invasion size 5 cm and 1‐3 positive nodes. Participants comprised 428 breast cancer patients with T1‐2 tumor and 1‐3 positive axillary nodes (pT1‐2 N1) treated using total mastectomy without radiotherapy. Correlations between clinicopathological characteristics and 10‐year Kaplan‐Meier estimates of locoregional recurrence‐free survival, disease‐free survival, and overall survival were retrospectively analyzed. Median follow‐up was 98 months. Locoregional recurrence was observed in 20 patients (4.7%), and distant recurrence was observed in 70 patients (16.4%). Disease‐free survival rate was 80.8%, and overall survival rate within the study period was 90%. Multivariate analysis demonstrated that favorable prognostic factors for locoregional recurrence‐free survival were the presence of chemotherapy and positive hormone receptor status, and for disease‐free survival were presence of chemotherapy, pT1 tumor, and single positive node. Physicians may consider these favorable prognostic factors in decision to eliminate PMRT from patients with the borderline indications.     

Disparities in reconstruction rates after mastectomy for ductal carcinoma in situ (DCIS): patterns of care and factors associated with the use of breast reconstruction for DCIS compared with invasive cancer

Background  

Many factors influence whether breast cancer patients undergo reconstruction after mastectomy. This study was undertaken to determine the patterns of care and variables associated with the use of reconstruction for ductal carcinoma in situ (DCIS) and to compare previous results for invasive carcinoma.     

Programmed death ligand 1 expression in prostate cancer cells is associated with deep changes of the tumor inflammatory infiltrate composition

Background

The main aim of this study was to investigate the putative correlation between the composition of intratumoral inflammatory infiltrate and the expression of programmed death ligand 1 (PD-L1) by prostate cancer cells. In addition, we evaluated the correlation between the expression of PD-L1 and PTX3.