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Breast Cancer

Breast cancer is the most common type of cancer among women, the risk of breast cancer increases with age, it is most common after the age of 50. Each breast has 15- 20 sections (lobes), each of which has many smaller sections (lobules). The lobes and lobules are connected by thin tubes (ducts). The most frequent type of breast cancer is that starting in the ducts (ductal cancer), other types include cancer beginning in the lobes or lobules (lobular carcinoma), less common is Inflammatory breast cancer which causes the breast to be red, and swollen. The incidence of breast cancer has been increasing in Western countries, the rate of increase has been faster in younger women, however, the cause of most breast cancers remains unknown. World-wide about 794,000 women are diagnosed with breast cancer each year.

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Information for Patients and the Public
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Latest Research Publications
Breast Cancer Organisations
Specialist Journals
Breast Cancer in Pregnancy
Breast Cancer Screening
Familial Breast Cancer
Male Breast Cancer
Paget's Disease of the Breast

Information Patients and the Public (42 links)

Information for Health Professionals / Researchers (15 links)

See also: Molecular Biology of Breast Cancer

Breast Cancer Organisations (11 links)

See also: National Cancer Organisations

Specialist Journals (12 links)

See also: Oncology Journals

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Poortmans PM, Collette S, Kirkove C, et al.
Internal Mammary and Medial Supraclavicular Irradiation in Breast Cancer.
N Engl J Med. 2015; 373(4):317-27 [PubMed] Related Publications
BACKGROUND: The effect of internal mammary and medial supraclavicular lymph-node irradiation (regional nodal irradiation) added to whole-breast or thoracic-wall irradiation after surgery on survival among women with early-stage breast cancer is unknown.
METHODS: We randomly assigned women who had a centrally or medially located primary tumor, irrespective of axillary involvement, or an externally located tumor with axillary involvement to undergo either whole-breast or thoracic-wall irradiation in addition to regional nodal irradiation (nodal-irradiation group) or whole-breast or thoracic-wall irradiation alone (control group). The primary end point was overall survival. Secondary end points were the rates of disease-free survival, survival free from distant disease, and death from breast cancer.
RESULTS: Between 1996 and 2004, a total of 4004 patients underwent randomization. The majority of patients (76.1%) underwent breast-conserving surgery. After mastectomy, 73.4% of the patients in both groups underwent chest-wall irradiation. Nearly all patients with node-positive disease (99.0%) and 66.3% of patients with node-negative disease received adjuvant systemic treatment. At a median follow-up of 10.9 years, 811 patients had died. At 10 years, overall survival was 82.3% in the nodal-irradiation group and 80.7% in the control group (hazard ratio for death with nodal irradiation, 0.87; 95% confidence interval [CI], 0.76 to 1.00; P=0.06). The rate of disease-free survival was 72.1% in the nodal-irradiation group and 69.1% in the control group (hazard ratio for disease progression or death, 0.89; 95% CI, 0.80 to 1.00; P=0.04), the rate of distant disease-free survival was 78.0% versus 75.0% (hazard ratio, 0.86; 95% CI, 0.76 to 0.98; P=0.02), and breast-cancer mortality was 12.5% versus 14.4% (hazard ratio, 0.82; 95% CI, 0.70 to 0.97; P=0.02). Acute side effects of regional nodal irradiation were modest.
CONCLUSIONS: In patients with early-stage breast cancer, irradiation of the regional nodes had a marginal effect on overall survival. Disease-free survival and distant disease-free survival were improved, and breast-cancer mortality was reduced. (Funded by Fonds Cancer; ClinicalTrials.gov number, NCT00002851.).

Whelan TJ, Olivotto IA, Parulekar WR, et al.
Regional Nodal Irradiation in Early-Stage Breast Cancer.
N Engl J Med. 2015; 373(4):307-16 [PubMed] Related Publications
BACKGROUND: Most women with breast cancer who undergo breast-conserving surgery receive whole-breast irradiation. We examined whether the addition of regional nodal irradiation to whole-breast irradiation improved outcomes.
METHODS: We randomly assigned women with node-positive or high-risk node-negative breast cancer who were treated with breast-conserving surgery and adjuvant systemic therapy to undergo either whole-breast irradiation plus regional nodal irradiation (including internal mammary, supraclavicular, and axillary lymph nodes) (nodal-irradiation group) or whole-breast irradiation alone (control group). The primary outcome was overall survival. Secondary outcomes were disease-free survival, isolated locoregional disease-free survival, and distant disease-free survival.
RESULTS: Between March 2000 and February 2007, a total of 1832 women were assigned to the nodal-irradiation group or the control group (916 women in each group). The median follow-up was 9.5 years. At the 10-year follow-up, there was no significant between-group difference in survival, with a rate of 82.8% in the nodal-irradiation group and 81.8% in the control group (hazard ratio, 0.91; 95% confidence interval [CI], 0.72 to 1.13; P=0.38). The rates of disease-free survival were 82.0% in the nodal-irradiation group and 77.0% in the control group (hazard ratio, 0.76; 95% CI, 0.61 to 0.94; P=0.01). Patients in the nodal-irradiation group had higher rates of grade 2 or greater acute pneumonitis (1.2% vs. 0.2%, P=0.01) and lymphedema (8.4% vs. 4.5%, P=0.001).
CONCLUSIONS: Among women with node-positive or high-risk node-negative breast cancer, the addition of regional nodal irradiation to whole-breast irradiation did not improve overall survival but reduced the rate of breast-cancer recurrence. (Funded by the Canadian Cancer Society Research Institute and others; MA.20 ClinicalTrials.gov number, NCT00005957.).

Kaufman SA, Harris EE, Bailey L, et al.
ACR Appropriateness Criteria® Ductal Carcinoma in Situ.
Oncology (Williston Park). 2015; 29(6):446-58, 460-1 [PubMed] Related Publications
Ductal carcinoma in situ (DCIS) is a breast neoplasm with potential for progression to invasive cancer. Management commonly involves excision, radiotherapy, and hormonal therapy. Surgical assessment of regional lymph nodes is rarely indicated except in cases of microinvasion or mastectomy. Radiotherapy is employed for local control in breast conservation, although it may be omitted for select low-risk situations. Several radiotherapy techniques exist beyond standard whole-breast irradiation (ie, partial-breast irradiation [PBI], hypofractionated whole-breast radiation); evidence for these is evolving. We present an update of the American College of Radiology (ACR) Appropriateness Criteria® for the management of DCIS. The ACR Appropriateness Criteria® are evidence-based guidelines for specific clinical conditions, which are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review includes an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi technique) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

Kim GE, Lee JS, Park MH, Yoon JH
Metastasis associated in colon cancer 1 predicts poor outcomes in patients with breast cancer.
Anal Quant Cytopathol Histpathol. 2015; 37(2):96-104 [PubMed] Related Publications
OBJECTIVE: To investigate whether metastasis associated in colon cancer 1 (MACC1) expression is a prognostic marker in breast cancer and to demonstrate the potential correlation between MACC1 and mitogen-activated protein kinase (MAPK) expression.
STUDY DESIGN: Immunohistochemical staining with anti-MACC1 and phospho-p44/42 MAPK antibodies was performed in 198 invasive breast carcinomas using tissue microarray.
RESULTS: Expression of MACC1 was detected in 109 (55.1%) of 198 invasive breast carcinomas. MACC1 expression was significantly higher in the metastatic relapse-positive group (87.8%, 36/41) than in the metastatic relapse-negative group (46.5%, 73/157) (p < 0.001). MACC1 expression was significantly correlated with phospho-p44/42 MAPK expression (p < 0.05). On univariate analysis a significant association was observed between MACC1 expression and decreased disease-free survival (p < 0.001) and overall survival (p = 0.001). On multivariate analysis MACC1 expression was one of the statistically significant independent risk factors for disease-free survival (p = 0.001).
CONCLUSION: MACC1 may serve as a new parameter for the prognostic prediction in patients with invasive breast carcinoma. MACC1 is likely to be involved in the regulation of MAPK cascades in invasive breast carcinoma.

Yamamoto-Ibusuki M, Arnedos M, André F
Targeted therapies for ER+/HER2- metastatic breast cancer.
BMC Med. 2015; 13:137 [PubMed] Free Access to Full Article Related Publications
The majority of breast cancers present with estrogen receptor (ER)-positive and human epidermal growth factor receptor (HER2)-negative features and might benefit from endocrine therapy. Although endocrine therapy has notably evolved during the last decades, the invariable appearance of endocrine resistance, either primary or secondary, remains an important issue in this type of tumor. The improvement of our understanding of the cancer genome has identified some promising targets that might be responsible or linked to endocrine resistance, including alterations affecting main signaling pathways like PI3K/Akt/mTOR and CCND1/CDK4-6 as well as the identification of new ESR1 somatic mutations, leading to an array of new targeted therapies that might circumvent or prevent endocrine resistance. In this review, we have summarized the main targeted therapies that are currently being tested in ER+ breast cancer, the rationale behind them, and the new agents and combinational treatments to come.

Travier N, Velthuis MJ, Steins Bisschop CN, et al.
Effects of an 18-week exercise programme started early during breast cancer treatment: a randomised controlled trial.
BMC Med. 2015; 13:121 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Exercise started shortly after breast cancer diagnosis might prevent or diminish fatigue complaints. The Physical Activity during Cancer Treatment (PACT) study was designed to primarily examine the effects of an 18-week exercise intervention, offered in the daily clinical practice setting and starting within 6 weeks after diagnosis, on preventing an increase in fatigue.
METHODS: This multi-centre controlled trial randomly assigned 204 breast cancer patients to usual care (n = 102) or supervised aerobic and resistance exercise (n = 102). By design, all patients received chemotherapy between baseline and 18 weeks. Fatigue (i.e., primary outcome at 18 weeks), quality of life, anxiety, depression, and physical fitness were measured at 18 and 36 weeks.
RESULTS: Intention-to-treat mixed linear model analyses showed that physical fatigue increased significantly less during cancer treatment in the intervention group compared to control (mean between-group differences at 18 weeks: -1.3; 95 % CI -2.5 to -0.1; effect size -0.30). Results for general fatigue were comparable but did not reach statistical significance (-1.0, 95%CI -2.1; 0.1; effect size -0.23). At 18 weeks, submaximal cardiorespiratory fitness and several muscle strength tests (leg extension and flexion) were significantly higher in the intervention group compared to control, whereas peak oxygen uptake did not differ between groups. At 36 weeks these differences were no longer statistically significant. Quality of life outcomes favoured the exercise group but were not significantly different between groups.
CONCLUSIONS: A supervised 18-week exercise programme offered early in routine care during adjuvant breast cancer treatment showed positive effects on physical fatigue, submaximal cardiorespiratory fitness, and muscle strength. Exercise early during treatment of breast cancer can be recommended. At 36 weeks, these effects were no longer statistically significant. This might have been caused by the control participants' high physical activity levels during follow-up.
TRIAL REGISTRATION: Current Controlled Trials ISRCTN43801571, Dutch Trial Register NTR2138. Trial registered on December 9th, 2009.

Humphries MP, Jordan VC, Speirs V
Obesity and male breast cancer: provocative parallels?
BMC Med. 2015; 13:134 [PubMed] Free Access to Full Article Related Publications
While rare compared to female breast cancer the incidence of male breast cancer (MBC) has increased in the last few decades. Without comprehensive epidemiological studies, the explanation for the increased incidence of MBC can only be speculated. Nevertheless, one of the most worrying global public health issues is the exponential rise in the number of overweight and obese people, especially in the developed world. Although obesity is not considered an established risk factor for MBC, studies have shown increased incidence among obese individuals. With this observation in mind, this article highlights the correlation between the increased incidence of MBC and the current trends in obesity as a growing problem in the 21(st) century, including how this may impact treatment. With MBC becoming more prominent we put forward the notion that, not only is obesity a risk factor for MBC, but that increasing obesity trends are a contributing factor to its increased incidence.

Turner NC, Ro J, André F, et al.
Palbociclib in Hormone-Receptor-Positive Advanced Breast Cancer.
N Engl J Med. 2015; 373(3):209-19 [PubMed] Related Publications
BACKGROUND: Growth of hormone-receptor-positive breast cancer is dependent on cyclin-dependent kinases 4 and 6 (CDK4 and CDK6), which promote progression from the G1 phase to the S phase of the cell cycle. We assessed the efficacy of palbociclib (an inhibitor of CDK4 and CDK6) and fulvestrant in advanced breast cancer.
METHODS: This phase 3 study involved 521 patients with advanced hormone-receptor-positive, human epidermal growth factor receptor 2-negative breast cancer that had relapsed or progressed during prior endocrine therapy. We randomly assigned patients in a 2:1 ratio to receive palbociclib and fulvestrant or placebo and fulvestrant. Premenopausal or perimenopausal women also received goserelin. The primary end point was investigator-assessed progression-free survival. Secondary end points included overall survival, objective response, rate of clinical benefit, patient-reported outcomes, and safety. A preplanned interim analysis was performed by an independent data and safety monitoring committee after 195 events of disease progression or death had occurred.
RESULTS: The median progression-free survival was 9.2 months (95% confidence interval [CI], 7.5 to not estimable) with palbociclib-fulvestrant and 3.8 months (95% CI, 3.5 to 5.5) with placebo-fulvestrant (hazard ratio for disease progression or death, 0.42; 95% CI, 0.32 to 0.56; P<0.001). The most common grade 3 or 4 adverse events in the palbociclib-fulvestrant group were neutropenia (62.0%, vs. 0.6% in the placebo-fulvestrant group), leukopenia (25.2% vs. 0.6%), anemia (2.6% vs. 1.7%), thrombocytopenia (2.3% vs. 0%), and fatigue (2.0% vs. 1.2%). Febrile neutropenia was reported in 0.6% of palbociclib-treated patients and 0.6% of placebo-treated patients. The rate of discontinuation due to adverse events was 2.6% with palbociclib and 1.7% with placebo.
CONCLUSIONS: Among patients with hormone-receptor-positive metastatic breast cancer who had progression of disease during prior endocrine therapy, palbociclib combined with fulvestrant resulted in longer progression-free survival than fulvestrant alone. (Funded by Pfizer; PALOMA3 ClinicalTrials.gov number, NCT01942135.).

Hasan R, Gavenonis SC, Shin MC
Utilizing digital breast tomosynthesis to improve accuracy of preoperative needle localization for surgical excisional biopsy.
Del Med J. 2015; 87(4):117-20 [PubMed] Related Publications
We describe a case of an 88-year-old female who presented for needle localization to undergo excisional biopsy of a subtle asymmetry in the left breast, with successful localization achieved using digital breast tomosynthesis. Initial attempts at localization under 2D mammography were inaccurate. Subsequent digital breast tomosynthesis application for triangulation resulted in better visualization of the target, and successful localization. Specimen radiography confirmed the lesion was accurately targeted and pathology revealed ductal carcinoma in situ. Needle localization guided by mammography and inherent limitations of 2D mammography are discussed, along with a literature review of tomosynthesis guided needle localization.

Egro FM, Pinell-White X, Hart AM, Losken A
The use of reduction mammaplasty with breast conservation therapy: an analysis of timing and outcomes.
Plast Reconstr Surg. 2015; 135(6):963e-971e [PubMed] Related Publications
BACKGROUND: Oncoplastic reduction mammaplasty is often used to prevent or correct breast conservation therapy deformities. The purpose of this review was to evaluate surgical outcomes, patient satisfaction, and aesthetic outcomes of this procedure when performed before or after radiation therapy.
METHODS: Breast cancer patients treated with breast conservation therapy and reduction mammaplasty between 2005 and 2012 were divided into immediate reconstruction, delayed immediate reconstruction, and delayed reconstruction. Greater than 6-month follow-up was required for inclusion. Patient demographics and clinical outcomes, including complications, patient satisfaction, and aesthetic result, were queried. Patient satisfaction was determined using the BREAST-Q survey. Postoperative photographs were used to rate aesthetic outcomes blinded to the timing of the procedure.
RESULTS: Patients in the immediate reconstruction group had fewer complications (immediate reconstruction, 20.5 percent; delayed immediate reconstruction, 33.3 percent; delayed reconstruction, 60.0 percent; p < 0.001) and asymmetry (immediate reconstruction, 8.5 percent; delayed immediate reconstruction, 44.4 percent; delayed reconstruction, 24.0 percent; p < 0.001), and required fewer procedures to complete the reconstruction (immediate reconstruction, 1.2; delayed immediate reconstruction, 2.4; delayed reconstruction, 2.2; p < 0.001). Delayed reconstruction resulted in higher complication and fat necrosis rates (immediate reconstruction, 0.9 percent; delayed immediate reconstruction, 0.0 percent; delayed reconstruction, 8.0 percent; p = 0.047). Although patient satisfaction and aesthetic outcomes were better in the immediate reconstruction group, this difference was not statistically significant.
CONCLUSIONS: Oncoplastic reduction techniques performed before radiation therapy result in fewer complications. Good patient satisfaction and aesthetic outcomes can be achieved when reduction is performed before or after radiation therapy, but patient selection and education are important.

Frederick MJ, Lin AM, Neuman R, et al.
Nipple-sparing mastectomy in patients with previous breast surgery: comparative analysis of 775 immediate breast reconstructions.
Plast Reconstr Surg. 2015; 135(6):954e-962e [PubMed] Related Publications
BACKGROUND: An increasing number of women are candidates for nipple preservation with mastectomy. It is unclear how previous breast surgery impacts nipple-sparing mastectomy and immediate breast reconstruction.
METHODS: A single-institution retrospective review was performed between June of 2007 and June of 2013.
RESULTS: Four hundred forty-four patients underwent 775 immediate breast reconstructions after nipple-sparing mastectomy. Of these, 160 patients and 187 reconstructions had previous breast surgery, including 154 lumpectomies, 27 breast augmentations, and six reduction mammaplasties. Two hundred eighty-four patients with 588 reconstructions without previous breast surgery served as the control group. The previous breast surgery patients were older (49.6 years versus 45.8 years; p < 0.001) but otherwise had similar demographics. Previous breast surgery reconstructions were more often unilateral, therapeutic, and associated with preoperative radiotherapy (p < 0.001 for each). Extension of breast scars was common with previous breast surgery, whereas the inframammary incision was most frequent if no scars were present (p < 0.001). Multivariate regression analysis showed that previous breast surgery was not a significant risk factor for ischemic complications or nipple loss. Subgroup analysis showed extension of prior irradiated incisions was predictive of skin flap necrosis (OR, 9.518; p = 0.05). A higher number of lumpectomy patients had preoperative radiotherapy (41 versus 11; p < 0.001), and patients with breast augmentation had more single-stage reconstructions (85.2 percent versus 62.9 percent; p = 0.02).
CONCLUSION: Nipple-sparing mastectomy and immediate reconstruction can be performed in patients with prior breast surgery with no significant increase in nipple loss or ischemic complications.

Chang EI, Chang EI, Soto-Miranda MA, et al.
Evolution of Bilateral Free Flap Breast Reconstruction over 10 Years: Optimizing Outcomes and Comparison to Unilateral Reconstruction.
Plast Reconstr Surg. 2015; 135(6):946e-953e [PubMed] Related Publications
BACKGROUND: There is an increasing trend for contralateral prophylactic mastectomy, but studies focusing on bilateral free flap breast reconstruction are lacking.
METHODS: A retrospective review was performed of all bilateral free flap breast reconstructions performed from 2000 to 2010.
RESULTS: Overall, 488 patients underwent bilateral breast reconstruction (bilateral immediate, n = 283; bilateral delayed, n = 93; and bilateral immediate/delayed, n = 112), which more than doubled from the years 2000-2005 to 2006-2010 [147 versus 341 (232.0 percent)]. Comparison of contralateral prophylactic mastectomy demonstrated a similar increase over the decade [139 versus 282 (203.9 percent)]. There was an increasing trend toward perforator flaps [70 versus 203 (290 percent)] compared to traditional transverse rectus abdominis myocutaneous flaps [99 versus 17 (17 percent)] between the first and second halves of the decade. Patients undergoing a bilateral immediate/delayed reconstruction were significantly more likely to undergo a revision (p = 0.05), particularly on the immediate reconstructed breast (OR, 1.59; p = 0.05). Delayed reconstruction and obesity were significantly associated with postoperative complications. Obesity, smoking, and radiation therapy significantly increased fat necrosis rates, 2.77 (p = 0.01), 2.31 (p = 0.03), and 2.38 times (p = 0.03), respectively. In comparison to unilateral reconstruction, bilateral reconstruction had significantly higher flap loss rates (p = 0.004), comparable donor-site complications, and equivalent rates of revisions.
CONCLUSIONS: There has been an increase in bilateral free flap breast reconstruction. Bilateral immediate/delayed reconstruction had higher revision rates of the prophylactic breast to achieve symmetry. Obesity, smoking, and radiation therapy were associated with increased complications, including fat necrosis, but successful reconstruction can be achieved with acceptable risks.

Hammond DC, Schmitt WP, O'Connor EA
Treatment of breast animation deformity in implant-based reconstruction with pocket change to the subcutaneous position.
Plast Reconstr Surg. 2015; 135(6):1540-4 [PubMed] Related Publications
UNLABELLED: Breast animation may be an unfortunate result of subpectoral implant-based reconstruction following mastectomy. This article reviews a novel approach to the treatment of animation deformity in cases of reconstruction, whereby the pectoralis major muscle is sutured down to the chest wall and the implant is transferred to the subcutaneous plane. A retrospective review was performed on 19 breasts undergoing pocket change. In selected cases, fat grafting was added to augment the soft-tissue framework around the implant. Demographics, operative details, outcomes, and complications were recorded. All 19 breasts had complete resolution of their animation deformity. Complications were seen in five breasts (26.3 percent). Four breasts (21.1 percent) developed Baker grade III or IV capsular contracture requiring capsulectomy that was curative. One seroma (5.3 percent) required in-office drainage. There were no visible implant deformities, infections, or implant removals. In appropriately selected patients, pocket change to a subcutaneous plane is a safe and effective technique for correction of severe animation deformity following implant-based breast reconstruction.

Gdalevitch P, Van Laeken N, Bahng S, et al.
Effects of nitroglycerin ointment on mastectomy flap necrosis in immediate breast reconstruction: a randomized controlled trial.
Plast Reconstr Surg. 2015; 135(6):1530-9 [PubMed] Related Publications
BACKGROUND: Mastectomy flap necrosis is a common complication of immediate breast reconstruction that impacts recovery time and reconstructive success. Nitroglycerin ointment is a topical vasodilator that has been shown to improve skin flap survival in an animal model. The objective of this study was to evaluate whether the application of nitroglycerin ointment to the breast skin after mastectomy and immediate reconstruction causes a decrease in the rate of mastectomy flap necrosis compared with placebo.
METHODS: This study was conducted as a randomized controlled trial and included patients aged 21 to 69 years undergoing mastectomy and immediate breast reconstruction at the University of British Columbia-affiliated hospitals (Vancouver, British Columbia, Canada). Patients with a medical history that precluded the administration of nitroglycerin were excluded from the study. The target sample size was 400 patients. Nitroglycerin ointment (45 mg) or a placebo was applied to the mastectomy skin at the time of surgical dressing.
RESULTS: The trial was stopped at the first interim analysis after 165 patients had been randomized (85 to the treatment group and 80 to the placebo group). Mastectomy flap necrosis developed in 27 patients (33.8 percent) receiving placebo and in 13 patients (15.3 percent) receiving nitroglycerin ointment; the between-group difference was 18.5 percent (p = 0.006; 95 percent CI, 5.3 to 31.0 percent). Postoperative complications were similar in both groups [nitroglycerin, 22.4 percent (19 of 85); placebo, 28.8 percent (23 of 80)].
CONCLUSIONS: In patients undergoing mastectomy and immediate reconstruction, there was a marked reduction in mastectomy flap necrosis in patients who received nitroglycerin ointment. Nitroglycerin ointment application is a simple, safe, and effective way to help prevent mastectomy flap necrosis.

Albornoz CR, Matros E, Lee CN, et al.
Bilateral Mastectomy versus Breast-Conserving Surgery for Early-Stage Breast Cancer: The Role of Breast Reconstruction.
Plast Reconstr Surg. 2015; 135(6):1518-26 [PubMed] Related Publications
BACKGROUND: Although breast-conserving surgery is oncologically safe for women with early-stage breast cancer, mastectomy rates are increasing. The objective of this study was to examine the role of breast reconstruction in the surgical management of unilateral early-stage breast cancer.
METHODS: A retrospective cohort study of women diagnosed with unilateral early-stage breast cancer (1998 to 2011) identified in the National Cancer Data Base was conducted. Rates of breast-conserving surgery, unilateral and bilateral mastectomy with contralateral prophylactic procedures (per 1000 early-stage breast cancer cases) were measured in relation to breast reconstruction. The association between breast reconstruction and surgical treatment was evaluated using a multinomial logistic regression, controlling for patient and disease characteristics.
RESULTS: A total of 1,856,702 patients were included. Mastectomy rates decreased from 459 to 360 per 1000 from 1998 to 2005 (p < 0.01), increasing to 403 per 1000 in 2011 (p < 0.01). The mastectomy rates rise after 2005 reflects a 14 percent annual increase in contralateral prophylactic mastectomies (p < 0.01), as unilateral mastectomy rates did not change significantly. Each percentage point of increase in reconstruction rates was associated with a 7 percent increase in the probability of contralateral prophylactic mastectomies, with the greatest variation explained by young age(32 percent), breast reconstruction (29 percent), and stage 0 (5 percent).
CONCLUSIONS: Since 2005, an increasing proportion of early-stage breast cancer patients have chosen mastectomy instead of breast-conserving surgery. This trend reflects a shift toward bilateral mastectomy with contralateral prophylactic procedures that may be facilitated by breast reconstruction availability.

Cox TR, Rumney RM, Schoof EM, et al.
The hypoxic cancer secretome induces pre-metastatic bone lesions through lysyl oxidase.
Nature. 2015; 522(7554):106-10 [PubMed] Related Publications
Tumour metastasis is a complex process involving reciprocal interplay between cancer cells and host stroma at both primary and secondary sites, and is strongly influenced by microenvironmental factors such as hypoxia. Tumour-secreted proteins play a crucial role in these interactions and present strategic therapeutic potential. Metastasis of breast cancer to the bone affects approximately 85% of patients with advanced disease and renders them largely untreatable. Specifically, osteolytic bone lesions, where bone is destroyed, lead to debilitating skeletal complications and increased patient morbidity and mortality. The molecular interactions governing the early events of osteolytic lesion formation are currently unclear. Here we show hypoxia to be specifically associated with bone relapse in patients with oestrogen-receptor negative breast cancer. Global quantitative analysis of the hypoxic secretome identified lysyl oxidase (LOX) as significantly associated with bone-tropism and relapse. High expression of LOX in primary breast tumours or systemic delivery of LOX leads to osteolytic lesion formation whereas silencing or inhibition of LOX activity abrogates tumour-driven osteolytic lesion formation. We identify LOX as a novel regulator of NFATc1-driven osteoclastogenesis, independent of RANK ligand, which disrupts normal bone homeostasis leading to the formation of focal pre-metastatic lesions. We show that these lesions subsequently provide a platform for circulating tumour cells to colonize and form bone metastases. Our study identifies a novel mechanism of regulation of bone homeostasis and metastasis, opening up opportunities for novel therapeutic intervention with important clinical implications.

Ellis H
Amputation of the breast.
J Perioper Pract. 2015 Jan-Feb; 25(1-2):27-8 [PubMed] Related Publications
Today we take for granted the blessing of anaesthesia and it is almost impossible for us to imagine the agonies that surgical patients underwent in the past. This description of a mastectomy, performed in 1720 by Lorenz Heister, Professor of Surgery and Anatomy in Altdorf in the republic of Nurnberg, (now part of Germany), gives a vivid idea of major surgery in those days. In this much shortened abstract from his lengthy report, which appears in the 1775 English edition of his textbook entitled 'Medical, Chirurgical and Anatomical cases and Observations' he discusses the preoperative preparation, the mastectomy itself, performed as quickly as possible and the tedious postoperative dressings of the inevitably suppurating wound.

Allinson VM, Dent J
Supportive care after breast cancer surgery.
Nurs Times. 2014 Oct 8-14; 110(41):20-3 [PubMed] Related Publications
Routine follow-up after treatment for breast cancer aims to monitor for recurrence, manage late effects of treatment and give patients information, support and reassurance. However, most symptoms of local recurrence are first identified by patients so time spent following up women who are essentially well may not be clinically beneficial or cost effective. To better use its resources, Calderdale and Huddersfield Foundation Trust developed a follow-up education programme for patients at low-to-moderate risk; after two years an audit showed it reduced overall patient anxiety and routine hospital appointments, maintained standards of care and provided patient with an effective support network.

Djurisic I, Santrac N, Buta M, et al.
Can we use frozen section analysis of sentinel lymph nodes mapped with methylene blue dye for decision making upon one-time axillary dissection in breast carcinoma surgery in developing countries?
J BUON. 2015 Mar-Apr; 20(2):492-7 [PubMed] Related Publications
PURPOSE: To evaluate the accuracy of intraoperative frozen section analysis (FSA) of sentinel lymph nodes (SLNs) mapped using methylene blue dye (MBD) and its usefulness for selecting patients with breast carcinomas and positive axillary lymph nodes (ALNs) for one-time axillary dissection.
METHODS: 152 female patients with T1/T2 breast carcinomas and clinically negative ALNs were selected for mapping using MBD (1%) from October 2010 to December 2011. Patients underwent FSA of mapped SLNs and ALN dissection. The accuracy of SLN-FSA was tested by comparing these findings with the definite histopathology (HP) of SLNs, as well as of other ALNs. Sensitivity, specificity, positive and negative predictive values were calculated.
RESULTS: There was a 98%-match between FSA and definite HP findings of SLNs, suggesting high accuracy of FSA in this series. None of 3 patients with false-negative SLNs on FSA had additional axillary nodal metastases. One out of 20 (5%) patients with metastases in other ALNs had "clear" SLNs, both on FSA and definite HP (false-negative). Accuracy reached 94.1%.
CONCLUSIONS: SLN-FSA enables adequate selection of patients for one-time axillary node dissection. MBD mapping technique is cheap, feasible and enables easy and precise detection of the first draining ALNs. Using FSA of SLNs mapped with MBD, patients with breast carcinoma benefit from complete surgical treatment during one hospitalization, the risk of undergoing anaesthesia twice is reduced, as well as the treatment cost, which is important in developing countries.

Kocic B, Filipovic S, Vrbic S, et al.
Stressful life events and breast cancer risk: a hospital-based case-control study.
J BUON. 2015 Mar-Apr; 20(2):487-91 [PubMed] Related Publications
PURPOSE: Elucidation of the factors contributing to the incidence of breast cancer is of crucial importance for the development of preventive or therapeutic strategies targeting the disease. Research on stress and breast cancer has been documented by various studies published over the years. In view of breast cancer importance as the most commonly occurring malignancy in females in Serbia, this study was undertaken to examine the association between stressful life events and breast cancer risk.
METHODS: The present hospital-based case-control study comprised 120 new breast cancer cases and 120 hospital controls matched with respect to age (± 2 years). This study used the Paykel Life Events Scale to obtain information about stressful life events in the years before diagnosis. The SPSS statistical package was used and odds ratios (OR) and 95% confidence intervals (95% CI) were calculated from multivariate conditional logistic regression model.
RESULTS: Multiple conditional logistic regression analysis revealed six independent predictors of breast cancer risk: experience of severe and moderate threats (first 25 life events from the scale) (OR=3.15, 95% CI=2.01-4.93), son's military service (OR=6.09, 95% CI=4.17-12.37), death of close family member (OR=7.98, 95% CI=2.18-9.14), moderate financial difficulties (OR=3.26, 95%CI=1.24-8.56), maternal death in childhood (OR=3.46, 95% CI=1.21-9.92) and serious financial difficulties (OR=3.55, 95% CI=1.20-10.52).
CONCLUSION: Stress exposure has been proposed to contribute to the etiology of breast cancer. There is a need for understanding the differing physiological effects of types or times of stress exposure.

Babacan T, Buyukhatipoglu H, Balakan O, et al.
Chemotherapy might not be beneficial in lymph node- negative, hormone-positive, and HER2-negative breast cancer patients: a long-term retrospective analysis.
J BUON. 2015 Mar-Apr; 20(2):479-86 [PubMed] Related Publications
INTRODUCTION: In lymph node-negative, hormone-positive, and Her2-negative breast cancer patients, the benefits of adding adjuvant chemotherapy to hormonal therapy continue to be debated, especially for low to intermediate grade and small tumors.
METHODS: Excluding patients with T4 disease, we retrospectively reviewed the records of patients with long-term follow-up at our center between 2003 and 2014. Among node-negative, hormone-positive and HER2-negative breast cancer patients, we compared two groups of patients: those given both chemotherapy (doxorubicin+cyclophosphamide) and hormonotherapy, and those prescribed hormonotherapy alone. The primary endpoints were progression-free (PFS) and overall survival (OS).
RESULTS: Overall, no difference was observed between these two treatment groups in either DFS or OS. However, for both outcomes, there was a trend towards improved DFS and OS favoring the hormone-only group.
CONCLUSIONS: In selected subgroups of breast cancer patients, administering adjuvant hormonal therapy alone seems to be at least as good if not better than combining hormonotherapy and chemotherapy.

Koukourakis G, Zacharias G, Petridis A
Evidence based whole breast hypo-fractionated radiation therapy in patients with early breast cancer.
J BUON. 2015 Mar-Apr; 20(2):473-8 [PubMed] Related Publications
PURPOSE: The aim of the current study was to evaluate the efficacy and tolerability of hypo-fractionated whole breast radiation therapy in patients with early breast cancer.
METHODS: Searching electronically PubMed and the Cochrane Central Register we made a comprehensive literature review regarding the randomized controlled phase III trials for hypo-fractionated radiation therapy in early breast cancer.
RESULTS: The collected and analyzed data showed that a short course of hypo-fractionated radiation therapy in early breast cancer patients is as effective as the conventional long course regarding tumor response as well as long term side effects.
CONCLUSION: More data are needed about the usage and integration of a boost treatment for higher-risk women receiving neo-adjuvant or adjuvant chemotherapy, or the results in special subgroups such as women with large breast size.

Arora S, Kumar R, Kaur H, et al.
Translocation and toxicity of docetaxel multi-walled carbon nanotube conjugates in mammalian breast cancer cells.
J Biomed Nanotechnol. 2014; 10(12):3601-9 [PubMed] Related Publications
Multi-walled-carbon nanotubes (MWNTs) are widely explored as carriers for drug delivery due to their facile transport through cellular membranes and are reportedly found to be effective against cancer. In the present study, we have evaluated cellular uptake of Docetaxel (DTX) conjugated MWNTs from human breast cancer cells (MCF-7 and MDA-mb-231) and have provided primary results on cytotoxicity of the same. Efficient internalization of the drug conjugate (DTX-MWNTs) inside the cell was corroborated with the help of confocal microscopy, transmission electron microscopy and flow cytometry. The comparison of cytotoxicity of the conjugate and DTX was done by MTT assay. Results of the study indicated increased efficacy of the conjugates over the drug in terms of their cytotoxicity. It was observed that such conjugation of drug to MWNTs can be explored as a strategy to improve therapeutic index of cytotoxic drugs such as DTX and thereby enriching cancer therapies of coming time.

Dauphine C, Reicher JJ, Reicher MA, et al.
A prospective clinical study to evaluate the safety and performance of wireless localization of nonpalpable breast lesions using radiofrequency identification technology.
AJR Am J Roentgenol. 2015; 204(6):W720-3 [PubMed] Related Publications
OBJECTIVE: The purpose of this study was to evaluate the safety and performance of localizing nonpalpable breast lesions using radiofrequency identification technology.
SUBJECTS AND METHODS: Twenty consecutive women requiring preoperative localization of a breast lesion were recruited. Subjects underwent placement of both a hook wire and a radiofrequency identification tag immediately before surgery. The radiofrequency identification tag was the primary method used by the operating surgeon to localize each lesion during excision, with the hook wire serving as backup in case of tag migration or failed localization. Successful localization with removal of the intended lesion was the primary outcome measured. Tag migration and postoperative infection were also noted to assess safety.
RESULTS: Twenty patients underwent placement of a radiofrequency identification tag, 12 under ultrasound guidance and eight with stereotactic guidance. In all cases, the radiofrequency identification tag was successfully localized by the reader at the level of the skin before incision, and the intended lesion was removed along with the radiofrequency identification tag. There were no localization failures and no postoperative infections. Tag migration did not occur before incision, but in three cases, occurred as the lesion was being retracted with fingers to make the final cut along the deep surface of the specimen.
CONCLUSION: In this initial clinical study, radiofrequency tags were safe and able to successfully localize nonpalpable breast lesions. Radiofrequency identification technology may represent an alternative method to hook wire localization.

Ha R, Jin B, Mango V, et al.
Breast cancer molecular subtype as a predictor of the utility of preoperative MRI.
AJR Am J Roentgenol. 2015; 204(6):1354-60 [PubMed] Related Publications
OBJECTIVE: The purpose of this study was to discern whether breast cancer molecular subtype, a known prognostic indicator, can be used to select patients with the highest likelihood of having clinically significant additional findings on breast MRI.
MATERIALS AND METHODS: A database review from January 2010 through December 2013 identified 299 patients who underwent preoperative breast MRI with tumors classifiable into molecular subtypes. Subtypes were classified on the basis of immunohistochemical staining surrogates as luminal A (hormone receptor [ER or PR] positive, ERBB2 [formerly HER2 or HER2/neu] negative, luminal B (hormone receptor positive, ERBB2 positive), ERBB2 (hormone receptor negative, ERBB2 positive), or basal (hormone receptor and ERBB2 negative). Univariate and multivariate logistic regression analyses were used to determine the association between subtype and additional breast MRI findings, including multicentric or multifocal disease, contralateral disease, chest wall involvement, skin and nipple involvement, and internal mammary and axillary lymphadenopathy.
RESULTS: The subtype distribution was luminal A, 70.6% (211/299); luminal B, 14.1% (42/299); ERBB2, 5.4% (16/299); and basal, 10.0% (30/299). ERBB2 and luminal B sub-types were more often associated with multicentric disease (25.0% and 26.2%), multifocal disease (37.5% and 35.7%), and axillary disease (50.0% and 45.2%) than were luminal A cancers (multicentric disease, 10.9%; multifocal disease 20.4%; axillary disease, 22.7%) (p < 0.001). In multivariate analysis, after control for patient age, tumor size, and nuclear grade, patients with ERBB2-overexpressing tumors were 2.4 times as likely as patients with luminal A tumors to have multicentric disease (p = 0.016), 2.0 times as likely to have multifocal disease (p = 0.024), 1.7 times as likely to have skin and nipple involvement (p = 0.013), and 1.9 times as likely to have axillary disease (p = 0.011).
CONCLUSION: Preoperative MRI may most benefit patients with tumors with ERBB2 overexpression because of the increased likelihood of the presence of additional disease.

Hruska CB, Conners AL, Jones KN, et al.
Diagnostic workup and costs of a single supplemental molecular breast imaging screen of mammographically dense breasts.
AJR Am J Roentgenol. 2015; 204(6):1345-53 [PubMed] Related Publications
OBJECTIVE: The purpose of this study was to examine additional diagnostic workup and costs generated by addition of a single molecular breast imaging (MBI) examination to screening mammography for women with dense breasts.
SUBJECTS AND METHODS: Women with mammographically dense breasts presenting for screening mammography underwent adjunct MBI performed with 300 MBq (99m)Tc-sestamibi and a direct-conversion cadmium-zinc-telluride dual-head gamma camera. All subsequent imaging tests and biopsies were tracked for a minimum of 1 year. The positive predictive value of biopsies performed (PPV3), benign biopsy rate, cost per patient screened, and cost per cancer detected were determined.
RESULTS: A total of 1651 women enrolled in the study. Among the 1585 participants with complete reference standard, screening mammography alone prompted diagnostic workup of 175 (11.0%) patients and biopsy of 20 (1.3%) and yielded five malignancies (PPV3, 25%). Results of combined screening mammography plus MBI prompted diagnostic workup of 279 patients (17.6%) and biopsy of 67 (4.2%) and yielded 19 malignancies (PPV3, 28.4%). The benign biopsy rates were 0.9% (15 of 1585) for screening mammography alone and 3.0% (48 of 1585) for the combination (p < 0.001). The addition of MBI increased the cost per patient screened from $176 for mammography alone to $571 for the combination. However, cost per cancer detected was lower for the combination ($47,597) than for mammography alone ($55,851).
CONCLUSION: The addition of MBI to screening mammography of women with dense breasts increased the overall costs and benign biopsy rate but also increased the cancer detection rate, which resulted in a lower cost per cancer detected than with screening mammography alone.

Lee J, Gordon PB, Whitman GJ
"Do unto others as you would have them do unto you": breast imagers' perspectives regarding screening mammography for others and for themselves--do they practice what they preach?
AJR Am J Roentgenol. 2015; 204(6):1336-44 [PubMed] Related Publications
OBJECTIVE: Our aim was to determine the screening recommendations that breast radiologists promote to average-risk patients and family or friends and do or would follow for themselves.
MATERIALS AND METHODS: A survey of breast radiologists in the United States collected data regarding their personal and practice backgrounds, their recommendations to others for mammography and clinical and self-breast examination, and their personal screening habits based on respondent sex. The radiologists were divided into three cohorts: women 40 years old or older (group 1), women younger than 40 years (group 2), and men (group 3). The distribution of responses for each question was summarized, and proportions of total radiologists and cohorts were computed.
RESULTS: Four hundred eighty-seven surveys were collected. None of the radiologists recommended biennial mammography for patients ages 50-74 years, 98% (477/487) recommended yearly mammography for patients 40 years old and older, and 99% (470/476) recommended yearly mammography for family and friends 40 years old and older. The most common reasons for variance were institutional policy or provider preferences. In group 1, 96% (191/198) have yearly mammography. In group 2, 100% (83/83) have or will have yearly mammography at age 40 years and beyond. In group 3, 97% (171/176) would have yearly mammography at age 40 years and beyond if they were women. Overall, 97% (445/457) of radiologists have or would have yearly mammography at age 40 years and beyond.
CONCLUSION: Nearly all (98%) of the radiologists recommend yearly mammography for average-risk women 40 years old and older and were consistent in that they "practice what they preach." Because radiologists diagnose all stages of breast cancer, their personal convictions should influence providers, patients, and the public when considering the U.S. Preventive Services Task Force screening guidelines.

Guo LS, Li HX, Li CY, et al.
Synergistic antitumor activity of vitamin D3 combined with metformin in human breast carcinoma MDA-MB-231 cells involves m-TOR related signaling pathways.
Pharmazie. 2015; 70(2):117-22 [PubMed] Related Publications
Metformin is usually used for the treatment of type 2 diabetes. Recently, many studies suggest that metformin and vitamin D have broad-spectrum antitumor activities. Our aim in this research was to study the effects of vitamin D3 combined with metformin on the apoptosis induction and its mechanisms in the human breast cancer cell line MDA-MB-231. Cell proliferation was measured by methylthiazol tetrazolium (MTT) assay. The morphology of cell apoptosis was observed after Hoechst 33342 staining. Here we show that vitamin D3 280 μg/ml or vitamin D3 300 μg/ml or vitamin D3 320 μg/ml seperately combined with metformin 15000 μg/ml exhibited synergistic effects on cell proliferation and apoptosis. The underlying anti-tumor mechanisms may involve m-TOR related pathways, which are related to activating expression of cleaved caspase-3, Bax and p-AMPK, as well as inhibiting expressions of p-Bcl-2, c-Myc, p-IGF-IR, p-mTOR, p-P70S6K, p-S6.

Milroy MJ
Breast cancer screening.
S D Med. 2015; Spec No:69-73 [PubMed] Related Publications
Decreasing breast cancer mortality represents a high priority for patients and their health care providers. Assessment of individual risk combined with discussion of risks and benefits of screening is essential in assisting patients in making their screening decisions. This article reviews the literature in order to provide primary care providers information regarding risk assessment, controversies regarding screening including age to start screening, best interval for screening, age to stop screening and methods to perform screening. Providers are encouraged to initiate this conversation with their patients.

Kerlikowske K, Zhu W, Tosteson AN, et al.
Identifying women with dense breasts at high risk for interval cancer: a cohort study.
Ann Intern Med. 2015; 162(10):673-81 [PubMed] Article available free on PMC after 19/05/2016 Related Publications
BACKGROUND: Twenty-one states have laws requiring that women be notified if they have dense breasts and that they be advised to discuss supplemental imaging with their provider.
OBJECTIVE: To better direct discussions of supplemental imaging by determining which combinations of breast cancer risk and Breast Imaging Reporting and Data System (BI-RADS) breast density categories are associated with high interval cancer rates.
DESIGN: Prospective cohort.
SETTING: Breast Cancer Surveillance Consortium (BCSC) breast imaging facilities.
PATIENTS: 365,426 women aged 40 to 74 years who had 831,455 digital screening mammography examinations.
MEASUREMENTS: BI-RADS breast density, BCSC 5-year breast cancer risk, and interval cancer rate (invasive cancer ≤12 months after a normal mammography result) per 1000 mammography examinations. High interval cancer rate was defined as more than 1 case per 1000 examinations.
RESULTS: High interval cancer rates were observed for women with 5-year risk of 1.67% or greater and extremely dense breasts or 5-year risk of 2.50% or greater and heterogeneously dense breasts (24% of all women with dense breasts). The interval rate of advanced-stage disease was highest (>0.4 case per 1000 examinations) among women with 5-year risk of 2.50% or greater and heterogeneously or extremely dense breasts (21% of all women with dense breasts). Five-year risk was low to average (0% to 1.66%) for 51.0% of women with heterogeneously dense breasts and 52.5% with extremely dense breasts, with interval cancer rates of 0.58 to 0.63 and 0.72 to 0.89 case per 1000 examinations, respectively.
LIMITATION: The benefit of supplemental imaging was not assessed.
CONCLUSION: Breast density should not be the sole criterion for deciding whether supplemental imaging is justified because not all women with dense breasts have high interval cancer rates. BCSC 5-year risk combined with BI-RADS breast density can identify women at high risk for interval cancer to inform patient-provider discussions about alternative screening strategies.
PRIMARY FUNDING SOURCE: National Cancer Institute.

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