Effect of Obesity on Presentation of Breast Cancer

Background Obesity has been shown to be associated with reduced survival in patients with invasive breast cancer (IBC), although the mechanisms for this finding are unclear. The objective of this study was to examine the effect of obesity on the presentation and pathologic staging of IBC. Methods From February 15, 2002, to February 15, 2004, all patients undergoing surgery for primary IBC at two institutions were enrolled in a prospective cohort study. National Institutes of Health criteria were used to categorize patients: normal or underweight (NW; body mass index <25 kg/m²), overweight (OW; body mass index 25–29.9 kg/m²), and obese or severely obese (OB; body mass index ≥30 kg/m²). Presentation and pathologic factors were then compared among groups. Results The study cohort consisted of 519 patients; 166 (32%) were NW, 177 (34%) were OW, and 176 (34%) were OB. OW (46%) and OB (39%) patients were more likely to be diagnosed with IBC via screening mammography compared with NW (31%) patients (P = .01), although no differences were found between groups with respect to previous use of screening mammography. Aggressive pathologic features, including lymph node metastases, advanced tumor-node-metastasis stage, and grade were found more commonly among OB patients. Conclusions OW and OB patients were more likely to receive a diagnosis via screening mammography, thus suggesting that mammography may play a more important role in OW and OB patients. Despite this, OB patients presented with larger, more advanced tumors; this may help to explain obesity-associated survival differences in IBC patients. This is important information given the prevalence of obesity in North America.     

Prolactin and Breast Cancer Etiology: An Epidemiologic Perspective

A number of epidemiologic studies of prolactin and breast cancer etiology have recently become available. Retrospective case-control studies have suggested a modest positive or null relationship between circulating prolactin concentrations and risk of breast cancer. However these studies are limited by small sample sizes and the collection of blood after case diagnosis. Several large prospective studies, in which blood was collected prior to diagnosis, have observed modest positive associations between prolactin and risk. In a pooled analysis of ~80% of the world’s prospective data, the relative risk (RR) comparing women in the top vs bottom quartile of prolactin levels was 1.3 (95% confidence interval (CI): 1.1, 1.6, p-trend = 0.002). The results were similar for premenopausal and postmenopausal women. Most notably, high prolactin levels were associated with a 60% increased risk of estrogen receptor (ER) positive tumors, but not with ER negative tumors. Limited genetic data suggest a role of polymorphisms in the prolactin and prolactin receptor genes in risk of breast cancer. Studies of survival have suggested that high pretreatment prolactin levels were associated with treatment failure, earlier recurrence, and worse overall survival. Parity and certain medications are the only confirmed factors associated with prolactin levels in women. Overall, epidemiologic data suggest that prolactin is involved in breast cancer etiology. Further research to better elucidate these associations and their underlying mechanisms is warranted.     

CyclinD1在不同分子亚型乳腺癌中的表达及其对预后的影响

目的检测cyclinD1在不同分子亚型乳腺癌中的表达,分析其表达与临床病理特征和预后的关系。方法采用免疫组织化学法检测175例乳腺癌组织标本中cyclinD1的表达情况,应用卡方检验分析cyclinD1在不同分子亚型乳腺癌中的表达,采用Spearman秩相关方法分析cyclinD1表达与临床病理特征的相关性,运用Kaplan．Meier生存曲线分析cyclinD1不同表达对预后的影响。结果①CyclinD1阳性表达在LuminalA型所占比例最高（P〈0．05）,而cyclinDI阴性表达在LuminalB型所占比例最高（P〈0．05）。②CyclinD1阳性表达与临床分期、组织学分级及PR无关（P〉0．05）,与淋巴结转移数目（rs=0．197,P〈0．01）、ER呈正相关（rs=0．139,P〈0．05）;cyclinD1阳性表达与Her-2呈负相关（rs=0．131,P〈0．05）。③CyclinD1阳性表达越强,无瘤生存时间越长（P〈0．05）。结论CyclinD1阳性表达与ER、Her-2及淋巴结转移数目有明显相关性,且其阳性表达提示相对良好的预后,可作为乳腺癌预后评估的参考指标。     

The German SUCCESS C Study - The First European Lifestyle Study on Breast Cancer

SUMMARY: Cohort trials have shown evidence that obesity and a low level of physical activity are not only associated with a higher risk of developing breast cancer, but also with an increased risk for recurrence and reduced survival in breast cancer patients. The SUCCESS C study is the first European trial to evaluate the effect of an intensive lifestyle intervention program on disease-free survival in women with early breast cancer and to examine the predictive value of selected biomarker candidates. A total of 3,547 women with early-stage, Her2/neu-negative breast cancer will be included. The first randomization will compare disease-free survival in patients treated with either 3 cycles of FEC (epirubicine, fluorouracil, cyclophosphamide), followed by 3 cycles of docetaxel or 6 cycles of docetaxel-cyclophosphamide, and thus assess the role of anthracycline-free chemotherapy. The second randomization compares disease-free survival in patients with a body mass index of 24-40 kg/m(2) receiving either a telephone-based individualized lifestyle intervention program aiming at moderate weight loss or general recommendations for a healthy lifestyle alone. In addition, the study will evaluate the predictive role of cancer-associated and obesity-related biomarkers for the prediction of disease recurrence and survival. This SUCCESS C trial will provide valuable information on the effects of a lifestyle intervention program on the prognosis of early breast cancer patients.     

原发局部晚期乳腺癌的治疗

目的：分析女性原发局部晚期乳腺癌治疗结果及预后，以确定更完善的治疗。方法：对１４７例进行回顾性研究，对治疗及多种因素与预后的相关性进行分析。结果：与预后相关的因素为腋淋巴结转移（Ｐ＜０．０５），治疗失败的原因是血行转移（Ｐ＜０．０５）。单纯手术治疗５年及１０年生存率分别为２６．７％、２０．０％，综合治疗５年及１０年生存率分别为５２．６％、４７．７％（Ｐ＜０．０１）。结论：应采用综合治疗     

Results of the First Austrian Multidisciplinary Expert Panel on Controversies in Local Treatment of Breast Cancer

At the first Austrian multidisciplinary expert panel on controversies in local treatment of breast cancer, 22 experts of all relevant disciplines discussed current areas of debate (surgery of the breast, surgery and pathology of the axilla, reconstructive surgery, radiotherapy, and imaging) in local therapy. The most controversial area of debate was the area of axillary surgery. The panel agreed that it was no longer necessary to perform completion axillary lymph node dissection (ALND) when micrometastases are diagnosed in the sentinel lymph node. The only prospective trial comparing patients with sentinel node macrometastases with or without completion ALND had to be terminated early due to failure in sufficient patient recruitment. As long as the frequently discussed issues have not been solved and in light of the lack of any clear level 1 evidence, the panel decided not to recommend omitting axillary dissection in patients with 1 or 2 macrometastases meeting the inclusion criteria of the ACOSOG Z0011 trial. The Austrian panel similarly decided not to recommend omitting axillary dissection in patients with macrometastases and low-risk breast cancer in general. These decisions reflect the increasing skepticism of the scientific community against rapidly shifting paradigms without sufficient and clear evidence.     

Breast Cancer and Transplantation

Breast cancer is an important cancer among solid organ transplant recipients. While the incidence of breast cancer in solid organ transplant recipients is comparable to the age‐matched general population, the outcomes are generally poor. Interventions such as cancer screening that preclude the development of late‐stage disease through early detection are not well studied, and clinical practice guidelines for cancer screening rely solely on recommendations from the general population. Among patients with a prior breast cancer history, disease recurrence after transplantation is a rare but fearful event. Once disease recurs, the risk of death is high. The focus of this review is to present the epidemiology of breast cancer in solid organ transplant recipients, screening and preventive strategies for those who may be at risk, novel genomic profiling for determining tumor progression, and the newer targeted interventions for recipients who have developed breast cancers after solid organ transplantation.     

The Impact of Nonvisualization of Sentinel Nodes on Lymphoscintigraphy in Breast Cancer

Background This study aimed at evaluating the relationship between the nonvisualization of sentinel nodes (SNs) at lymphoscintigraphy and the intraoperative detection rate, radioactive counts in vivo, and histological status of SNs.Methods Two hundred eighty patients with infiltrating breast carcinoma (T0, T₁/T₂) underwent preoperative lymphoscintigraphy before gamma probe–guided SN biopsy.Results The surgical identification rate with a gamma probe was 84.6% (56 of 280) in lymphoscintigraphy-negative patients and 93.2% (224 of 280) in lymphoscintigraphy-positive patients (P < .05) after two subdermal periareolar injections. The average number of SNs per patient was 1.7 in lymphoscintigraphy-negative patients and 2.2 in lymphoscintigraphy-positive patients (P < .01), as assessed by gamma detection. The mean age of lymphoscintigraphy-negative patients was 62 ± 10 years, versus 55 ± 13 years for lymphoscintigraphy-positive patients (P < .001). The median radioactive count in dissected SNs identified by gamma detection was 204 cps (range, 4–618 cps) in lymphoscintigraphy-negative patients, versus 606 cps (range, 43–16,928 cps) in lymphoscintigraphy-positive patients (P < .001). The rate of macrometastatic SNs was 40% in lymphoscintigraphy-negative patients, versus 30% in lymphoscintigraphy-positive patients (not significant), whereas the size of involved SNs was 16.6 mm in lymphoscintigraphy-negative patients, versus 13.1 in lymphoscintigraphy-positive patients (P < .05). The micrometastasis detection rate in SNs from lymphoscintigraphy-negative patients was 6.25%, versus 23.3% in lymphoscintigraphy-positive patients (P < .01).Conclusions Negative lymphoscintigraphy was observed in 20% of patients and was more frequent in elderly patients. Negative lymphoscintigraphy was predictive of a lower surgical identification rate and fewer detected SNs. These SNs had fewer micrometastases, were fairly large, and tended to harbor metastases.     

The Relevance of Mouse Models to Understanding the Development and Progression of Human Breast Cancer

Mouse modeling of human breast cancer has developed tremendously over the past ten years. Human breast cancer is characterized by enormous biological diversity and, collectively, the new models have come much closer to encompassing this diversity. They have provided a deeper understanding of the fundamental events that mediate the initiation, development, and progression of breast cancer, and they offer new opportunities to develop and test strategies to treat and, perhaps, even prevent the disease. This chapter reviews the historical development of mouse models of breast cancer and highlights some of their major strengths, weaknesses, and contributions.     

Manual of Recommendations for the Diagnosis, Therapy, and Follow-Up of Patients with Breast Cancer of the Tumor Center Munich - a Regional Hands-On Publication

The revised 11th edition of the Manual of Recommendations for the Diagnosis, Therapy, and Follow-Up of Patients with Breast Cancer of the publications series of the Tumor Center Munich (Tumorzentrum München, TZM) is an excellent example of a regional hands-on publication which, while based on national and international guidelines, does not replace these. By virtue of countless additions and revisions in the course of 10 editions, the 'blue tumor manual for breast cancer' has matured into a hands-on reference work which throughout Germany has found its place on the desks of physicians, and has thus gained a reputation reaching far beyond the TZM. The reputation of this manual is on the one hand founded on the professional competence of the individual authors and project group members. The great strength of the project group, however, surely lies in the broad spectrum of expertise of more than 180 experts of all kinds of specialties, whose continuing interdisciplinary exchange in the course of the present revision has again led to a result which is arousing interest far beyond Munich. This article summarizes some of the TZM project group's own positions on data collection, prevention, adjuvant systemic therapy, and follow-up treatment in an exemplary fashion.     

Analysis of Clinical Features and Outcome of 356 Triple-Negative Breast Cancer Patients in China

BACKGROUND: The purpose of this study was to investigate the clinicopathological features and analyze the prognostic factors of triple-negative breast cancer (TNBC). PATIENTS AND METHODS: The clinical data of 1,788 breast cancer patients was collected and analyzed. The Kaplan-Meier method was used to estimate survival. Multivariate analysis of the prognostic factors for survival was performed using the Cox regression model. RESULTS: Patients with TNBC exhibited characteristics significantly differing from those with non-TNBC. There was a higher proportion of patients with age < 35 years, stage III disease, tumor size > 5 cm, lymph node positivity, and histological grade 3. The 5-year disease-free survival (DFS) rates of TNBC and non-TNBC patients were 75.7 and 79.6%, respectively (p < 0.05). 5-year overall survival (OS) was 86.6 and 93.5%, respectively (p < 0.05). In multivariate Cox regression analysis, the independent prognostic factors for shorter DFS were age < 35 years (hazard ratio (HR) 2.105), positive lymph nodes (HR 7.039), histological grade 3 (HR 1.841), and for shorter OS positive lymph nodes (HR 4.626). CONCLUSION: The proportion of TNBC in breast cancer in China is higher than in other areas. TNBC is correlated with younger age, larger tumor size, positive lymph nodes, higher clinical stage and histological grade, and lower DFS and OS, which is consistent with previous reports.     

Impact of Surgery on Survival in Stage IV Breast Cancer

We aimed to assess retrospectively the survival outcome in patients with stage IV breast cancer who underwent surgery. In a retrospective, nonrandomized study of stage IV breast cancer patients diagnosed in a single institution between 2000 and 2012, we assessed patient's survival in the context of baseline characteristics. A total 678 patients with metastatic breast cancer were included; 412 (60.77%) underwent surgery for the primary tumor (Surgery group), and 266 (39%) did not underwent surgery for the primary tumor (Nonsurgery group), with a median follow‐up of 41 months. Patients in the Surgery group had longer survival (41 versus 27 months, p < 0.0029). The 5‐year survival rate for Surgery group was 34% compared with 14% for the Nonsurgery group. A multivariate analysis revealed surgery (p = 0.0003), large tumor size (p = 0.0195), ER‐positive (p < 0.0001), and metastasis at presentation (p = 0.0032) were prognostic variables. Loco‐regional surgery does confer a survival advantage in stage IV breast cancer, however, selection bias cannot be excluded, a well‐designed and powerful randomized, controlled trial would be valuable to answer whether surgery can improve survival.     

基质细胞衍化因子-1的表达及其与乳腺癌患者预后的关系

目的探讨基质细胞衍化因子-1(SDF-1)在不同细胞系及乳腺癌组织和正常乳腺组织中的表达,并分析SDF-1的表达水平与乳腺癌患者预后的关系。方法选择乳腺癌细胞系、成纤维细胞系、血管内皮细胞系,利用RT-PCR方法分析SDF-1mRNA的表达。采用免疫组织化学染色和实时定量PCR测定120例乳腺癌组织和32例正常乳腺组织中SDF-1的表达。通过SPSS统计软件对所得结果行统计学分析。结果SDF-1的表达见于人胚胎肺成纤维细胞系、某些乳腺癌细胞系(MDA-MB435s、MDA-MB436、MCF7)及乳腺癌和正常乳腺组织。淋巴结有转移者SDF-1mRNA的表达水平为399.00±210.00,淋巴结无转移者为0.89±0.47(P=0.048)。预后不良者(出现肿瘤局部复发、远处转移和因乳腺癌死亡者)较无疾病存活者SDF-1mRNA水平明显增高,为670.00±346.00vs0.83±0.35(P=0.01)。SDF-1mRNA的表达水平与患者的总存活率和无瘤存活率有关,P值分别为0.01和0.035。结论SDF-1mRNA的表达既可见于基质细胞也可见于乳腺癌细胞。SDF-1的表达水平与乳腺癌患者有无淋巴结转移、预后和存活密切相关。SDF-1可作为乳腺癌患者预后判断的一项指标。     

Influence of Family History of Breast or Ovarian Cancer on Pathological Complete Response and Long-Term Prognosis in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy

PurposeIn breast cancer, a pathological complete response (pCR) has been described as generally resulting in a favorable prognosis. However, there are subgroups, such as patients with a mutation in BRCA1 or BRCA2, in which the effect of pCR on the prognosis is suspected to be weaker. Patients with a family history of breast and/or ovarian cancer may therefore react differently in relation to pCR and prognosis, and this is investigated in this study.Patients and MethodsBreast cancer patients were identified from a clinical breast cancer registry. The study subjects had been treated with neoadjuvant chemotherapy from 2001 to 2018 and their pathological and clinical information as well as medical family history were available. They were considered to have a positive family history if they had at least 1 first-degree relative with breast and/or ovarian cancer. Multivariate logistic regression analyses were performed to study the association between family history, pCR (ypT0; ypN0), and disease-free survival (DFS).ResultsOf 1,480 patients, 228 (15.4%) had a positive family history. The pCR rates were 24.9% in all patients, and 24.4% and 27.6% in those without/with a family history, respectively. Family history was not associated with a higher pCR rate (adjusted odds ratio [OR] 1.23; 95% confidence interval [CI] 0.85–1.76; p = 0.27) or a different disease-free survival (DFS; adjusted hazard ratio [HR] 1.15; 95% CI 0.88–1.52; p = 0.30). pCR did not affect the prognosis differently in relation to family history.ConclusionsIn this retrospective analysis, family history was not associated with pCR and DFS. pCR improved survival, independently of family history.     

Nutrition and breast cancer

The major risk factors for breast cancer are hormone-related, and the only well-established diet-related risk factors for breast cancer are obesity and alcohol consumption. Obesity increases breast cancer risk in postmenopausal women by around 30%, probably by increasing serum concentrations of bioavailable oestradiol. Moderate alcohol intakes increase breast cancer risk by about 7% per alcoholic drink per day, perhaps also by increasing oestrogen levels. Populations with high fat intakes generally have high rates of breast cancer, but studies of individual women have not confirmed an association of high fat diets with breast cancer risk. Phyto-oestrogens can affect hormone metabolism, but data on phyto-oestrogen consumption and breast cancer risk are inconsistent. Nutrition might affect breast cancer risk by altering levels of growth factors such as insulin-like growth factor-I. Current dietary advice should be to avoid obesity, limit alcohol intake, and maintain a varied diet.     

Incidence of Lymph Node Metastasis and its Impact on Long-term Prognosis in Clinically Localized Prostate Cancer

Background: Pelvic lymph node dissection (PLND) is an important staging method for men with clinically localized prostate cancer. We report our experience with staging PLND and the impact of lymph node metastasis on long-term prognosis.
Methods: One hundred forty-eight consecutive patients who underwent staging PLND for clinically localized prostate cancer were retrospectively studied. Patients were evaluated for the presence and number of lymph node metastases, treatment (prostatectomy vs. radiotherapy), and endocrine therapy, and analyzed with respect to disease progression and survival. The mean follow-up period was 52.9 months (range, 2.3 to 165.8 months).
Results: Thirty-two patients (21.6%) had pelvic lymph node metastases, the incidence of which markedly decreased from 32.3% in 1982 to 1987 to 6.7% in 1994 to 1997. The intervals to disease progression and cancer death were significantly shorter in patients with positive lymph nodes ( P < 0.001). In stage D1 disease, patients who underwent a radical prostatectomy tended to be free of progression longer than those receiving radiotherapy or conservative therapy ( P = 0.0546). Other factors, such as early endocrine therapy, the extent of lymph node involvement and the Gleason score of the primary tumor did not predict disease progression or survival.
Conclusion: These data suggest a decreasing trend in the incidence of lymph node metastasis in the PSA era. Although longer disease-free intervals were observed in radical prostatectomy-treated patients, the impact of an aggressive approach to stage D1 disease awaits further studies.     

Prognostic Evaluation of Breast Cancer Patients with Evident Bone Marrow Metastasis

In this study, we aimed to evaluate the clinicopathologic characteristics and prognosis of breast cancer (BC) patients with symptomatic bone marrow metastasis (BMM). Fifty‐four BC patients, including patients with and without BMM, were evaluated retrospectively. In particular, the clinicopathologic features and survival of the patients with BMM (n = 27) were assessed and compared with the patients without BMM. All of the patients with BMM also had osseous metastases, and bone was the first site for distant recurrence in the majority of patients in the study group. Anemia was the most frequent symptom at presentation. The median time to BMM was 36.1 months (range 1.6–70.5 months, 95% CI). HER2(+) patients developed BMM earlier than HER2(?) patients (3.2 versus 38.3 months, 95% CI; p = 0.05). Patients with advanced disease at the time of initial BC diagnosis developed BMM earlier than patients with early disease (p = 0.04). Time to development of BMM was significantly shorter in tumors with perinodal infiltration (p = 0.001) and multicentric focus (p = 0.025). Median survival time after the diagnosis of apparent BMM was 6.43 months. Survival after BMM diagnosis in patients with grade III tumors was significantly shorter than in patients with grade I–II tumors (1.43 versus 5.36 months, 95% CI; p < 0.001). Systemic therapy after BMM diagnosis significantly prolonged survival (17.3 versus 0.93 months, 95% CI; p < 0.001). Hormone receptor‐positive, high‐grade, advanced‐stage tumors at the time of initial BC diagnosis were more common in patients with BMM. Invasive lobular histology was also more frequent in patients with BMM. In conclusion, the presence of hormone receptor‐positive, multicentric, grade III, advanced‐stage tumors may be important risk factors for the development of evident BMM in BC patients. Systemic single‐agent chemotherapy can prolong survival in these patients. However, multicenter analyses are required to verify these findings.     

The Role of Oncoplastic Surgery in Breast Cancer

The authors discuss the objectives of oncoplastic surgery in breast cancer management. Indications and advantages are summarised. Some surgical techniques are described.

The authors report their own experience with oncoplastic surgery (26 patients who had immediate breast reconstruction after tumorectomy, and 126 patients who had lumpectomy alone. Oncoplastic surgery was characterised by a wider excision, with negative margins in all cases. In isolated breast conservative tumorectomy, 20% of the margins were positive, requiring re-excision or radical mastectomy.

Oncoplastic surgery is preferred especially in younger patients with smaller breasts, since it is less cosmetically mutulating and allows complete tumor resection with save margins.