Breast Cancer
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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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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).

Ujunwa FA, Chinawa JM, Enemuo A, Ikefuna AN
An unusual presentation of non-Hodgkins lymphoma: a case report.
Niger J Med. 2014 Apr-Jun; 23(2):176-7 [PubMed] Related Publications
BACKGROUND: Breast lymphoma is an uncommon disease with poor clinical outcome. The rarity of the disease is related to relatively small amount of lymphoid tissues in the breast. The prognosis usually depends on the stage at presentation.
OBJECTIVE: To highlight an uncommon presentation of Non-Hodgkin's Lymphoma.
CONCLUSION: Non-Hodgkin's lymphoma can affect the breast. A high index of suspicion and prompt histological diagnosis are needed for effective management.

Related: Non Hodgkin's Lymphoma

Dodiyi-Manuel A, Wakama IE
Predispositions of carcinoma of the breast: a review.
Niger J Med. 2014 Jan-Mar; 23(1):7-12 [PubMed] Related Publications
BACKGROUND: Breast cancer is an ancient disease and the leading malignancy affecting women. The incidence is high in developed countries while it is low but increasing in developing countries. The aim of this review is to update and summarize the predisposing factors of breast cancer.
METHODS: Literature review was conducted using goggle search engine and hinari. Selected papers were taken for further reference and using books from author's collection.
RESULTS: The cause of breast cancer is unknown but predisposing factors have been identified to indicate increase susceptibility to developing the disease.
CONCLUSION: Breast is the commonest malignancy affecting women worldwide.

Related: Male Breast Cancer

Ishizuna K, Ninomiya J, Ogawa T, et al.
Locally advanced breast cancer with bleeding - two cases effectively treated with bevacizumab plus weekly paclitaxel.
Gan To Kagaku Ryoho. 2014; 41(5):637-40 [PubMed] Related Publications
Bleeding is one of the serious adverse events of bevacizumab (BV). In our report, two patients had locally advanced breast cancer with bleeding. They received BV plus weekly paclitaxel (PTX), and good local control was observed. Case 1: The patient was a 50-year-old postmenopausal woman. She had left-sided breast cancer (T4cN2cM1 [bone]-stageIV) that was negative for estrogen receptor (ER), negative for progesterone receptor(PgR), and 1+for human epidermal growth factor receptor 2 (HER2). The patient began receiving different regimens of chemotherapy: 5-fluorouracil (5-FU), epirubicin (EPI), and cyclophosphamide(CPA), (FEC); PTX; docetaxel (DTX); and gemcitabine (GEM) plus PTX. Subsequently, she received BV plus PTX. The tumor was markedly reduced in size at the completion of 2 cycles. Bleeding and exudate were also reduced. The patient had a partial response until the sixth cycle, and good local control was obtained. However, the patient had progressive disease at the completion of 8 cycles. Therefore, therapy was changed to capecitabine(CAP)plus CPA, but the patient died one year after she began treatment with BV plus PTX. Case 2: The patient was a 76-year-old postmenopausal woman. She had right-sided breast cancer (T4bN3bM1[lung]-stageIV) that was negative for ER, negative for PgR, and 0 for HER2. The patient began receiving different regimens of chemotherapy: EPI and CPA (EC); and PTX. Subsequently, she received BV plus PTX. The tumor was markedly reduced in size at the completion of 2 cycles. Bleeding and exudate were also reduced. The patient had a partial response until the third cycle, and good local control was obtained. However, the patient had progressive disease at the completion of 4 cycles. Therefore, therapy was changed to CAP and DTX, but the patient died six months after she began treatment with BV plus PTX.

Related: Paclitaxel Bevacizumab (Avastin)

Lemieux J, Provencher L, Laflamme C
Survey about the use of scalp cooling to prevent alopecia during breast cancer chemotherapy treatment in Canada.
Can Oncol Nurs J. 2014; 24(2):102-8 [PubMed] Related Publications
Alopecia is a side effect of chemotherapies used in breast cancer. Scalp cooling is a technique preventing alopecia, but its use remains controversial. We conducted a survey about knowledge of scalp cooling and interest in conducting a randomized clinical trial (RCT). An invitation was sent to 1,022 participants and a total of 139 individuals responded to the survey. The majority knew about the existence of scalp cooling. Ninety per cent thought that an RCT was needed and would participate. The survey revealed different potential problems associated with the increased chair time, limited space, and safety. We concluded that an RCT is needed and that the trial must include evaluation on the impact on health care system resources and safety.

Related: Cancer Treatments and Hair Loss Canada

Zheng W, Hu W, Wang Y, et al.
Comparative analysis of gene expression profiles in basal-like carcinomas of the breast.
Anal Quant Cytol Histol. 2014; 36(2):82-90 [PubMed] Related Publications
OBJECTIVE: To compare basal-like breast carcinoma (BLBC) gene expression profiles to normal mammary epithelium in order to determine the characteristic gene expression patterns associated with the tumor.
STUDY DESIGN: The gene expression profiles of 12 cases of BLBC were analyzed using a human mRNA genome expression profiling chip containing 48,804 probes in an attempt to characterize molecular mechanism involved in the carcinogenesis of BLBC.
RESULTS: The identified 99 genes were upregulated more than fourfold fold-change (FC) value over their levels in normal mammary ductal epithelial cells, and 43 genes were downregulated to less than fivefold FC value compared to normal epithelial cells. Verification of selected genes by semiquantitative reverse transcription polymerase chain reaction was performed to confirm the expression data obtained by microarray analysis. Most of the abnormal expressed genes were related to DNA binding, transcription and its factor, cell receptors, cell signals and transmitted proteins, metabolism-related proteins, and protein synthesis-related genes.
CONCLUSION: The difference of gene expression profiles might be of benefit for selecting the relative genes of the basal-like carcinoma as the therapy target and to further the understanding of the development of BLBC.

Related: Basal Cell Carcinoma

Ayadi-Kaddour A, Khadhar A, Mlika M, et al.
Fibroadenoma in an ectopic vulvar breast gland: a common neoplasm in an uncommon site.
Pathologica. 2014; 106(1):32-4 [PubMed] Related Publications
Ectopic breast tissue is defined as glands located outside of the breast. It can be found anywhere along the milk line extending from the axilla to the groin, and can occur in the vulva. Ectopic breast tissue should be excised because it may develop benign or malignant pathologic processes. Less than 40 cases of fibroadenoma in the vulva have been reported in the literature. We report a case of a 37-year-old woman presenting a solitary vulvar mass. The mass was excised completely, and histology demonstrated an ectopic breast fibroadenoma. This is one of the few reports on the benign pathologies of vulvar mammary glands.

Nedved D, Connor C, Sharma P, O'Neil M
Collision tumour of the breast composed of Merkel cell carcinoma and invasive ductal carcinoma: a case report.
Pathologica. 2014; 106(1):16-21 [PubMed] Related Publications
We report a case of a 71-year-old female with a palpable breast mass. Pathologic evaluation of the breast mass showed a unique collision tumour with a high-grade invasive and in-situ ductal carcinoma component and a high-grade neuroendocrine carcinoma component. The neuroendocrine component turned out to be Merkel cell carcinoma (MCC), with immunohistochemical confirmation. To the best of our knowledge, this is the first case report of a collision tumour with ordinary ductal carcinoma and MCC in the breast.

Related: Merkel Cell Carcinoma

Elsberger B, Roxburgh CS, Horgan PG
Is there a role for surgical resections of hepatic breast cancer metastases?
Hepatogastroenterology. 2014 Jan-Feb; 61(129):181-6 [PubMed] Related Publications
Breast cancer accounts for over 12,000 deaths in the UK annually; 12% of women develop hepatic metastases receiving systemic therapy as standard treatment. Hepatic resection has been proposed as a potentially curative alternative. Current literature was reviewed and evaluated for hepatic resection on breast cancer liver metastases by conducting a literature search across Ovid Medline, Embase and PubMed. Twenty-one studies were included in the review. All were retrospective, single centre case series. Eighteen studies reported results for ten or more patients. Only three studies reported results for over 50 patients. The time-span for the individual series ranged from 9-20 years. Generally, liver resection for breast cancer liver metastases is a safe procedure with only two post-operative deaths reported. Median time to recurrence was low (10-36 months). Overall 5-year survival ranged from 12-75%. Poorer prognosis correlated with increasing size and number of metastases, extrahepatic spread and short time span from primary surgery to the development of further metastases. Current literature does not establish clearly, who should undergo a hepatic resection for breast cancer metastasis. But it seems that hepatic resection should be considered as a therapeutic option for limited volume liver metastasis in high-risk breast cancer patients. However, prospective cohort studies are required to establish the role of hepatic resection for breast cancer metastasis.

Stout NK, Lee SJ, Schechter CB, et al.
Benefits, harms, and costs for breast cancer screening after US implementation of digital mammography.
J Natl Cancer Inst. 2014; 106(6):dju092 [PubMed] Article available free on PMC after 01/06/2015 Related Publications
BACKGROUND: Compared with film, digital mammography has superior sensitivity but lower specificity for women aged 40 to 49 years and women with dense breasts. Digital has replaced film in virtually all US facilities, but overall population health and cost from use of this technology are unclear.
METHODS: Using five independent models, we compared digital screening strategies starting at age 40 or 50 years applied annually, biennially, or based on density with biennial film screening from ages 50 to 74 years and with no screening. Common data elements included cancer incidence and test performance, both modified by breast density. Lifetime outcomes included mortality, quality-adjusted life-years, and screening and treatment costs.
RESULTS: For every 1000 women screened biennially from age 50 to 74 years, switching to digital from film yielded a median within-model improvement of 2 life-years, 0.27 additional deaths averted, 220 additional false-positive results, and $0.35 million more in costs. For an individual woman, this translates to a health gain of 0.73 days. Extending biennial digital screening to women ages 40 to 49 years was cost-effective, although results were sensitive to quality-of-life decrements related to screening and false positives. Targeting annual screening by density yielded similar outcomes to targeting by age. Annual screening approaches could increase costs to $5.26 million per 1000 women, in part because of higher numbers of screens and false positives, and were not efficient or cost-effective.
CONCLUSIONS: The transition to digital breast cancer screening in the United States increased total costs for small added health benefits. The value of digital mammography screening among women aged 40 to 49 years depends on women's preferences regarding false positives.

Related: Cancer Screening and Early Detection USA

Yu Q, Yi J, Zhao G, Zhang Y
Effect of vascular network and nanoparticles on heat transfer and intracellular ice formation in tumor tissues during cryosurgery.
Cryo Letters. 2014 Mar-Apr; 35(2):95-100 [PubMed] Related Publications
BACKGROUND: Cryosurgery is a physical therapy of tumor treatment which is welcome in clinics for its minimally invasive advantage. However, the high recurrence rate makes the conventional cryosurgery unsatisfactory, which needs adjuvant treatment such as introduction of nanoparticles.
OBJECTIVE: This study is to examine the effects of vascular network and MgO nanoparticles on heat transfer and intracellular ice formation in tumor tissues during cryosurgery.
METHOD: We developed a multi-scale model to study the efficiency of cryosurgery, including the macro-level (mass tumor tissue) heat transfer and the micro-level (tumor cells) probability of intracellular ice formation (PIF). The model is used to examine the effects of fractal vascular network (VN) and nanoparticles with different concentration on heat transfer and PIF during cryosurgery in the breast cancer tissue (MCF-7 cells). The nucleation rate kinetic parameter and the thermodynamic parameter of MCF-7 cells are determined by nonlinear curve-fitting the published experimental data, and then the probability of intracellular ice formation of the picked points in the tumor tissue are determined using the classic model for intracellular ice nucleation with the simulated thermal profiles at those points during cryosurgery.
RESULTS AND CONCLUSION: The introduction of nanoparticles have significantly enhanced the heat transfer in the mass tumor tissue and increased the PIF of tumor cells, indicating the nanocryosurgery is more efficient than conventional cryosurgery.

Related: Angiogenesis and Cancer

Pendse AA, Edgerly CH, Fedoriw Y
Hemolytic anemia and metastatic carcinoma: case report and literature review.
Lab Med. 2014; 45(2):132-5 [PubMed] Related Publications
Hemolytic anemia can complicate the development of a variety of solid tumors and hematologic malignancies. Although patients may have an established diagnosis with documented metastases, microangiopathic hemolytic anemia (MAHA) can be a presenting feature of an occult malignancy. Prompt diagnosis is essential because conditions that mimic the symptoms of MAHA, including thrombotic thrombocytopenic purpura, have different prognoses and therapeutic options. Although the exact pathogenesis is not yet delineated, we present herein a case of cancer-associated MAHA and discuss the known pathways that can contribute to the initiation and propagation of hemolytic anemia in patients with cancer. The patient is a 69-year-old woman with breast carcinoma that had metastasized to her rectum, urinary bladder, and brain. She eventually developed progressive decline in her functional status, with intermittent epistaxis and melena. The results of laboratory studies revealed hemolytic anemia and thrombocytopenia; results of a bone-marrow biopsy confirmed the involvement by metastatic carcinoma. The patient received red blood cell and platelet transfusions and was discharged to hospice care after clinical stabilization. She died soon thereafter.

Qureshi S, Ghazanfar S, Iqbal S, et al.
Results of level-II oncoplasty in breast cancer patients: an early experience from a tertiary care hospital in Pakistan.
J Pak Med Assoc. 2014; 64(3):309-15 [PubMed] Related Publications
OBJECTIVE: To assess the oncologic and cosmetic outcomes for breast cancer patients who underwent breast conservation therapy using Level II oncoplasty techniques.
METHODS: The prospective, non-randomised and descriptive study was conducted at the Department of Surgery, Unit IV of Civil Hospital, Karachi, from December 2009 to November 2011 in which 21 consecutive women with breast carcinoma who underwent wide local excision with remodeling mammoplasty were enrolled. All patients were reviewed by the surgeon and medical oncologist every 3 months for the first year. A grading system of 5-1 (excellent to poor) was employed and those with 3 or more were considered to have acceptable results.
RESULTS: The mean patient age was 45.38 +/- 10.09 years (range: 26-70); 11 (52.3%) were premenopausal and 10 (47.7%) were postmenopausal; and 5 (27.8%) had family history of breast cancer. The mean size of the tumour determined by histology was 59.9 +/- 3.18 mm (range: 25-150). Eight (30%) patients received preoperative chemotherapy to downsize the tumour. Three (14.2%) patients received preoperative radiotherapy. Mean operative time was 1.59 +/- 0.52 hours (range: 1-2.5 hours). Mean volume of breast tissue excised from the breast containing the tumour was 545.27 +/- 412.06 cm3 (range: 43.70-1456). Assessment of excision margins showed no tumour at the margins of 19 (90.4%) patients. Two (9.5%) patients had close but negative margins. The mean hospital stay was 7.10 +/- 3.30 days (range: 4-15). There were early complications in 4 (19%) patients. One (4.76%) patient had late complications. Two (9.5%) patients developed tumour recurrence; both had an ipsilateral tumour recurrence. None of the patients developed metastases and one died of cardiac problem. Twenty (95.2%) patients had an acceptable post-surgical cosmetic result.
CONCLUSION: Level II oncoplasty was a safe option in breast conservation allowing large-sized and difficult-location tumour excision with good cosmetic outcome in the study group. There is a need to increase the awareness and acceptance of this new technique not only amongst patients but also doctors.

Takagi K, Moriguchi T, Miki Y, et al.
GATA4 immunolocalization in breast carcinoma as a potent prognostic predictor.
Cancer Sci. 2014; 105(5):600-7 [PubMed] Related Publications
Transcriptional GATA factors are known lineage selector genes and regulate a variety of biological processes including specification and differentiation of tissues. In the present study, we examined expression profiles of six GATA factor genes in invasive ductal carcinomas (IDC) of the breast using microarray analysis (n = 20) and found that GATA4 expression was closely correlated with recurrence in patients. Because the significance of GATA4 has remained largely unknown in breast carcinoma, we further immunolocalized GATA4 in ductal carcinoma in situ (DCIS) of the breast (n = 48) and IDC (n = 163). GATA4 immunoreactivity was detected in the nuclei of carcinoma cells and was positive in 27% of DCIS and 31% of IDC cases. GATA4 status was significantly associated with nuclear grade and van Nuys classification in DCIS and was positively associated with distant metastasis, histological grade and HER2 status, but negatively correlated with progesterone receptor labeling index in IDC. Subsequent multivariate analysis demonstrated that GATA4 status was an independent prognostic factor for both disease-free and breast cancer-specific survival of IDC patients. All of these results indicate that GATA4 plays important roles in the progression of breast carcinoma from an early stage and that immunohistochemical GATA4 status is considered a potent prognostic factor in human breast cancer patients.

Goble RN, Drukteinis JS, Lee MC, et al.
Early experience with ultrasound features after intrabeam intraoperative radiation for early stage breast cancer.
J Surg Oncol. 2014; 109(8):751-5 [PubMed] Related Publications
BACKGROUND: Intraoperative radiation therapy (IORT) is an emerging option for partial breast radiotherapy in select women with early stage breast cancer. We assessed short-term clinical and sonographic findings after breast conservation (BCT) and IORT.
METHODS: An IRB-approved, single institution retrospective chart review was conducted of patients (pts) treated with BCT/IORT from 1/2011 to 6/2012. Follow-up clinical breast exams and ultrasounds (US) obtained 6 and 12 months after BCT/IORT were retrospectively reviewed by a single breast radiologist (JD) for sonographic findings. P values were calculated using McNemar's test, Wilcoxon Rank Sum Test, and Chi-square.
RESULTS: Seventy-one pts underwent BCT/IORT and 38 pts had an US. All 38 pts had a seroma, 10/38 (26%) pts were symptomatic. Eighteen pts had deep tissue closure (DTC) of the lumpectomy cavity with 5/18 (28%) DTC pts being symptomatic at follow-up versus 5/33 (15%) without DTC (P = 0.296). At 6 months, DTC resulted in smaller seroma cavity volumes compared to those without DTC (P = 0.03).
CONCLUSION: Presence of a seroma is commonplace post BCT/IORT; symptomatic seromas are uncommon. DTC generated smaller seromas. Longer follow-up with serial US performed in all BCT/IORT pts could be considered to document natural progression/regression of symptoms and seromas.

Tummers QR, Verbeek FP, Schaafsma BE, et al.
Real-time intraoperative detection of breast cancer using near-infrared fluorescence imaging and Methylene Blue.
Eur J Surg Oncol. 2014; 40(7):850-8 [PubMed] Article available free on PMC after 01/07/2015 Related Publications
BACKGROUND: Despite recent developments in preoperative breast cancer imaging, intraoperative localization of tumor tissue can be challenging, resulting in tumor-positive resection margins during breast conserving surgery. Based on certain physicochemical similarities between Technetium((99m)Tc)-sestamibi (MIBI), an SPECT radiodiagnostic with a sensitivity of 83-90% to detect breast cancer preoperatively, and the near-infrared (NIR) fluorophore Methylene Blue (MB), we hypothesized that MB might detect breast cancer intraoperatively using NIR fluorescence imaging.
METHODS: Twenty-four patients with breast cancer, planned for surgical resection, were included. Patients were divided in 2 administration groups, which differed with respect to the timing of MB administration. N = 12 patients per group were administered 1.0 mg/kg MB intravenously either immediately or 3 h before surgery. The mini-FLARE imaging system was used to identify the NIR fluorescent signal during surgery and on post-resected specimens transferred to the pathology department. Results were confirmed by NIR fluorescence microscopy.
RESULTS: 20/24 (83%) of breast tumors (carcinoma in N = 21 and ductal carcinoma in situ in N = 3) were identified in the resected specimen using NIR fluorescence imaging. Patients with non-detectable tumors were significantly older. No significant relation to receptor status or tumor grade was seen. Overall tumor-to-background ratio (TBR) was 2.4 ± 0.8. There was no significant difference between TBR and background signal between administration groups. In 2/4 patients with positive resection margins, breast cancer tissue identified in the wound bed during surgery would have changed surgical management. Histology confirmed the concordance of fluorescence signal and tumor tissue.
CONCLUSIONS: This feasibility study demonstrated an overall breast cancer identification rate using MB of 83%, with real-time intraoperative guidance having the potential to alter patient management.

Pertuzumab. Promising for some women with metastatic breast cancer, but more assessment needed.
Prescrire Int. 2014; 23(148):95 [PubMed] Related Publications
Adding trastuzumab to chemotherapy can prolong overall survival among women with metastatic or locally recurrent unresectable breast cancer that overexpresses HER-2 protein. Pertuzumab (Perjeta, Roche) is a monoclonal antibody that targets HER-2. It has a different binding site from that of trastuzumab, another anti-HER-2 antibody. Pertuzumab has been authorised in the European Union as an adjunct to the trastuzumab + docetaxel combination. A double-blind randomised placebo-controlled trial involving 808 carefully selected patients (including two men), followed for about 2.5 years, showed that the addition of pertuzumab to trastuzumab + docetaxel prolonged overall survival: it was estimated that the 3-year survival rate increased by 10% to 15%. Median progression-free survival was 6 months longer in the pertuzumab group. Addition of pertuzumab did not aggravate cardiac toxicity among patients with a low cardiovascular risk at baseline. In contrast, adding pertuzumab increased the incidence of potentially severe diarrhoea, mucocutaneous disorders (rash, dry skin, mucosal inflammation) and febrile neutropenia. In practice, these results are interesting but they must be confirmed in other comparative trials before recommending routine use of pertuzumab.

O'Sullivan CC, Connolly RM
Pertuzumab and its accelerated approval: evolving treatment paradigms and new challenges in the management of HER2-positive breast cancer.
Oncology (Williston Park). 2014; 28(3):186-94, 196 [PubMed] Related Publications
The addition of trastuzumab, a monoclonal antibody to human epidermal growth factor receptor 2 (HER2), to standard chemotherapy in patients with HER2-positive breast cancer has resulted in major improvements in breast cancer outcomes, including improved survival, in both the adjuvant and metastatic settings. However, some patients experience disease relapse despite adjuvant trastuzumab-containing therapy, and resistance to trastuzumab develops in the majority of patients in the metastatic setting. An understanding of the molecular mechanisms underlying trastuzumab resistance has aided the development of novel HER2-targeted therapies. In June 2012, the HER2 dimerization inhibitor pertuzumab was approved by the US Food and Drug Administration (FDA) for use with chemotherapy and trastuzumab in the first-line treatment of metastatic HER2-positive breast cancer. In September 2013, accelerated approval was granted for use of pertuzumab in the neoadjuvant setting, representing a landmark decision by the FDA. This article discusses the development of pertuzumab to date, with a particular focus on the accelerated approval decision. We highlight the need to identify reliable biomarkers of sensitivity and resistance to HER2-targeted therapy, which would make possible the individualization of treatment for patients with HER2-positive breast cancer.

Related: Signal Transduction USA

Vucemilo T, Skoko M, Sarcević B, et al.
The level of serum pro-matrix metalloproteinase-2 as a prognostic factor in patients with invasive ductal breast cancer.
Coll Antropol. 2014; 38(1):135-40 [PubMed] Related Publications
This paper analyses data of 150 female patients undergoing surgical treatment for invasive ductal breast cancer at the University Hospital for Tumors from January 2006 to January 2007. The control group consisted of 50 healthy women. The patients were classified into three groups, depending on their tumor differentiation, i.e. grade I, II and III tumor groups. Each group consisted of 50 patients. Traditional prognostic factors including: age, tumor size and differentiation grade, axillary lymph node status, presence of distant metastases, steroid receptor findings, vascular invasion of the primary tumor, presence of an extensive intraductal component (EIC) in the primary tumor, HER-2 protein expression were evaluated. Both the patients' and controls' serum levels of proMMP-2 (pro-matrix metalloproteinase-2) were assessed using the ELISA method. The aim of the study was to assess pathohistological prognostic factors and the level of serum proMMP-2 in the three patient groups and the controls, compare the relationship between the prognostic factors and the level of serum proMMP-2 in the patient groups, and upon the results, determine possible features of proMMP-2 as a prognostic factor in breast cancer patients. The study results showed no difference in proMMP-2 concentrations between the three patient groups and the controls. No statistically significant difference in the serum proMMP-2 concentration was found between the patient groups, although the grade III group values were the highest showing a trend toward statistical significance. Comparison of proMMP-2 and prognostic factors revealed a statistically significant correlation between proMMP-2 and age in patients with histologic grade I tumors. There was no statistically significant correlation between circulating proMMP-2 and other pathohistological prognostic factors.

Related: MMP2

Geller BM, Bogart A, Carney PA, et al.
Educational interventions to improve screening mammography interpretation: a randomized controlled trial.
AJR Am J Roentgenol. 2014; 202(6):W586-96 [PubMed] Related Publications
OBJECTIVE: The objective of our study was to conduct a randomized controlled trial of educational interventions that were created to improve performance of screening mammography interpretation.
MATERIALS AND METHODS: We randomly assigned physicians who interpret mammography to one of three groups: self-paced DVD, live expert-led educational seminar, or control. The DVD and seminar interventions used mammography cases of varying difficulty and provided associated teaching points. Interpretive performance was compared using a pretest-posttest design. Sensitivity, specificity, and positive predictive value (PPV) were calculated relative to two outcomes: cancer status and consensus of three experts about recall. The performance measures for each group were compared using logistic regression adjusting for pretest performance.
RESULTS: One hundred two radiologists completed all aspects of the trial. After adjustment for preintervention performance, the odds of improved sensitivity for correctly identifying a lesion relative to expert recall were 1.34 times higher for DVD participants than for control subjects (95% CI, 1.00-1.81; p = 0.050). The odds of an improved PPV for correctly identifying a lesion relative to both expert recall (odds ratio [OR] = 1.94; 95% CI, 1.24-3.05; p = 0.004) and cancer status (OR = 1.81; 95% CI, 1.01-3.23; p = 0.045) were significantly improved for DVD participants compared with control subjects, with no significant change in specificity. For the seminar group, specificity was significantly lower than the control group (OR relative to expert recall = 0.80; 95% CI, 0.64-1.00; p = 0.048; OR relative to cancer status = 0.79; 95% CI, 0.65-0.95; p = 0.015).
CONCLUSION: In this randomized controlled trial, the DVD educational intervention resulted in a significant improvement in screening mammography interpretive performance on a test set, which could translate into improved interpretative performance in clinical practice.

Related: Cancer Screening and Early Detection USA

Mesurolle B, Perez JC, Azzumea F, et al.
Atypical ductal hyperplasia diagnosed at sonographically guided core needle biopsy: frequency, final surgical outcome, and factors associated with underestimation.
AJR Am J Roentgenol. 2014; 202(6):1389-94 [PubMed] Related Publications
OBJECTIVE: The purposes of this article were to review the mammographic and sonographic features of breast masses yielding atypical ductal hyperplasia (ADH) at sonographically guided biopsy, evaluate the surgical pathology outcome of these lesions, and determine whether clinical or imaging features can be used to predict upgrade to malignancy.
MATERIALS AND METHODS: Among 6325 sonographically guided biopsies (2003- 2010) (14-gauge cores), 56 yielded the diagnosis of ADH (0.9%). Six patients were excluded (lost to follow-up). Fifty lesions were surgically excised in 45 patients. Mammographic and sonographic features were analyzed in consensus by two radiologists using the BI-RADS lexicon.
RESULTS: Forty-five patients (mean age, 56 years; 12 < 50 years; six with synchronous breast carcinoma) had 50 ADH lesions (median size, 0.6 cm). Surgical excision yielded malignancy in 28 cases (56% underestimation rate). Among 42 mammograms (47 lesions), 30 lesions were identified (30/47, 64%) as masses (12/30, 40%), asymmetric densities (10/30, 33%), microcalcifications (4/30, 13%), and architectural distortions (4/30, 13%). Sonographically, most lesions appeared as hypoechoic masses (64%, 30/47) with irregular shape (51%, 24/47), microlobulated margins (49%, 23/47), no posterior acoustic feature (25/47, 53%), abrupt interface (70%, 33/47), and parallel orientation (57%, 27/47). No mammographic and sonographic features were associated with malignant outcome, whereas age less than 50 years (p = 0.03) and synchronous malignancy (p = 0.03) were associated with malignant outcome.
CONCLUSION: ADH diagnosed at sonographically guided 14-gauge core needle biopsy shows a high underestimation rate. Synchronous carcinoma or age less than 50 years is associated with malignant outcome.

Loving VA, Edwards DB, Roche KT, et al.
Monte Carlo simulation to analyze the cost-benefit of radioactive seed localization versus wire localization for breast-conserving surgery in fee-for-service health care systems compared with accountable care organizations.
AJR Am J Roentgenol. 2014; 202(6):1383-8 [PubMed] Related Publications
OBJECTIVE: In breast-conserving surgery for nonpalpable breast cancers, surgical reexcision rates are lower with radioactive seed localization (RSL) than wire localization. We evaluated the cost-benefit of switching from wire localization to RSL in two competing payment systems: a fee-for-service (FFS) system and a bundled payment system, which is typical for accountable care organizations.
MATERIALS AND METHODS: A Monte Carlo simulation was developed to compare the cost-benefit of RSL and wire localization. Equipment utilization, procedural workflows, and regulatory overhead differentiate the cost between RSL and wire localization. To define a distribution of possible cost scenarios, the simulation randomly varied cost drivers within fixed ranges determined by hospital data, published literature, and expert input. Each scenario was replicated 1000 times using the pseudorandom number generator within Microsoft Excel, and results were analyzed for convergence.
RESULTS: In a bundled payment system, RSL reduced total health care cost per patient relative to wire localization by an average of $115, translating into increased facility margin. In an FFS system, RSL reduced total health care cost per patient relative to wire localization by an average of $595 but resulted in decreased facility margin because of fewer surgeries.
CONCLUSION: In a bundled payment system, RSL results in a modest reduction of cost per patient over wire localization and slightly increased margin. A fee-for-service system suffers moderate loss of revenue per patient with RSL, largely due to lower reexcision rates. The fee-for-service system creates a significant financial disincentive for providers to use RSL, although it improves clinical outcomes and reduces total health care costs.

Related: Brachytherapy USA

Sung JS, Li J, Da Costa G, et al.
Preoperative breast MRI for early-stage breast cancer: effect on surgical and long-term outcomes.
AJR Am J Roentgenol. 2014; 202(6):1376-82 [PubMed] Related Publications
OBJECTIVE: The purpose of this study was to evaluate the effect of the use of preoperative breast MRI on surgical and long-term outcomes among women with early-stage breast cancer undergoing breast conservation therapy.
MATERIALS AND METHODS: A retrospective review yielded the cases of 174 women with stage 0, I, or II breast cancer who underwent preoperative MRI between 2000 and 2004. A control group of 174 patients who did not undergo preoperative MRI before breast conservation therapy was matched by age, histopathologic finding, stage, and surgeon. Features compared included breast density, presence of mammographically occult disease, margin status, lymph node involvement, lymphovascular invasion, extensive intraductal component, hormone receptor status, and use of adjuvant therapy. Outcomes, including rates of reexcision, ipsilateral recurrence, and disease-free survival, were compared by Kaplan-Meier methods and the log-rank test.
RESULTS: Patients referred for preoperative breast MRI were more likely to have extremely dense breasts (28% vs 6%, p < 0.0001) and mammographically occult cancer (24% vs 9%, p = 0.0003). The two groups had identical rates of final negative margins, lymph node involvement, lymphovascular invasion, extensive intraductal component status, positive hormone receptor results, and systemic adjuvant therapy. Fewer patients in the preoperative MRI group needed reexcision (29% vs 45%, p = 0.02). The median follow-up period after treatment was 8 years. There was no significant difference in locoregional recurrence (p = 0.33) or disease-free survival (p = 0.73) rates between the two groups.
CONCLUSION: Reexcision rates among patients with early breast cancer undergoing conservation therapy were lower among women who underwent preoperative breast MRI. There was no statistically significant effect of the use of preoperative MRI on rates of locoregional recurrence or disease-free survival.

Related: USA

Lee JM, Hays JL, Annunziata CM, et al.
Phase I/Ib study of olaparib and carboplatin in BRCA1 or BRCA2 mutation-associated breast or ovarian cancer with biomarker analyses.
J Natl Cancer Inst. 2014; 106(6):dju089 [PubMed] Article available free on PMC after 01/06/2015 Related Publications
BACKGROUND: Olaparib has single-agent activity against breast/ovarian cancer (BrCa/OvCa) in germline BRCA1 or BRCA2 mutation carriers (gBRCAm). We hypothesized addition of olaparib to carboplatin can be administered safely and yield preliminary clinical activity.
METHODS: Eligible patients had measurable or evaluable disease, gBRCAm, and good end-organ function. A 3 + 3 dose escalation tested daily oral capsule olaparib (100 or 200mg every 12 hours; dose level1 or 2) with carboplatin area under the curve (AUC) on day 8 (AUC3 day 8), then every 21 days. For dose levels 3 to 6, patients were given olaparib days 1 to 7 at 200 and 400 mg every 12 hours, with carboplatin AUC3 to 5 on day 1 or 2 every 21 days; a maximum of eight combination cycles were permitted, after which daily maintenance of olaparib 400mg every12 hours continued until progression. Dose-limiting toxicity was defined in the first two cycles. Peripheral blood mononuclear cells were collected for polymorphism analysis and polyADP-ribose incorporation. Paired tumor biopsies (before/after cycle 1) were obtained for biomarker proteomics and apoptosis endpoints.
RESULTS: Forty-five women (37 OvCa/8 BrCa) were treated. Dose-limiting toxicity was not reached on the intermittent schedule. Expansion proceeded with olaparib 400mg every 12 hours on days 1 to 7/carboplatin AUC5. Grade 3/4 adverse events included neutropenia (42.2%), thrombocytopenia (20.0%), and anemia (15.6%). Responses included 1 complete response (1 BrCa; 23 months) and 21 partial responses (50.0%; 15 OvCa; 6 BrCa; median = 16 [4 to >45] in OvCa and 10 [6 to >40] months in BrCa). Proteomic analysis suggests high pretreatment pS209-eIF4E and FOXO3a correlated with duration of response (two-sided P < .001; Pearson's R (2) = 0.94).
CONCLUSIONS: Olaparib capsules 400mg every 12 hours on days 1 to 7/carboplatin AUC5 is safe and has activity in gBRCAm BrCa/OvCa patients. Exploratory translational studies indicate pretreatment tissue FOXO3a expression may be predictive for response to therapy, requiring prospective validation.

Related: Carboplatin Ovarian Cancer

Brown-Glaberman U, Dayao Z, Royce M
HER2-targeted therapy for early-stage breast cancer: a comprehensive review.
Oncology (Williston Park). 2014; 28(4):281-9 [PubMed] Related Publications
The discovery of human epidermal growth factor receptor 2 (HER2) and its role in the biology of breast cancer, and the subsequent development of HER2-targeted therapies, have dramatically improved clinical outcomes for millions of women with early-stage and advanced HER2-positive breast cancer. This review discusses the treatment of primary, nonmetastatic HER2-positive breast cancer in the adjuvant and neoadjuvant settings--settings in which tremendous progress has been made. Novel approaches, including the use of combinations of HER2-targeted therapies, are examined. Future challenges include refining such treatments, reducing toxicity in those who have low-risk disease, and simultaneously developing innovative therapies for patients who remain at high risk for relapse with existing treatment options.

Rack B, Schindlbeck C, Jückstock J, et al.
Circulating tumor cells predict survival in early average-to-high risk breast cancer patients.
J Natl Cancer Inst. 2014; 106(5) [PubMed] Related Publications
BACKGROUND: Circulating tumor cells (CTCs) have been shown to predict reduced survival outcomes in metastatic breast cancer.
METHODS: CTCs were analyzed in 2026 patients with early breast cancer before adjuvant chemotherapy and in 1492 patients after chemotherapy using the CellSearch System. After immuno-magnetic enrichment for cells expressing the epithelial-cell adhesion molecule, CTCs were defined as nucleated cells expressing cytokeratin and lacking CD45. The patients were followed for a median of 35 months (range = 0-54). Kaplan-Meier analyses and the log-rank test were used for survival analyses. All statistical tests were two-sided.
RESULTS: Before chemotherapy, CTCs were detected in 21.5% of patients (n = 435 of 2026), with 19.6% (n = 136 of 692) of node-negative and 22.4% (n = 299 of 1334) of node-positive patients showing CTCs (P < .001). No association was found with tumor size, grading, or hormone receptor status. After chemotherapy, 22.1% of patients (n = 330 of 1493) were CTC positive. The presence of CTCs was associated with poor disease-free survival (DFS; P < .0001), distant DFS (P < .001), breast cancer-specific survival (P = .008), and overall survival (OS; P = .0002). CTCs were confirmed as independent prognostic markers in multivariable analysis for DFS (hazard ratio [HR] = 2.11; 95% confidence interval [CI] = 1.49 to 2.99; P < .0001) and OS (HR = 2.18; 95% CI = 1.32 to 3.59; P = .002). The prognosis was worst in patients with at least five CTCs per 30 mL blood (DFS: HR = 4.51, 95% CI = 2.59 to 7.86; OS: HR = 3.60, 95% CI = 1.56 to 8.45). The presence of persisting CTCs after chemotherapy showed a negative influence on DFS (HR = 1.12; 95% CI = 1.02 to 1.25; P = .02) and on OS (HR = 1.16; 95% CI = 0.99 to 1.37; P = .06) CONCLUSIONS: These results suggest the independent prognostic relevance of CTCs both before and after adjuvant chemotherapy in a large prospective trial of patients with primary breast cancer.

Related: Cyclophosphamide Epirubicin Fluorouracil Docetaxel Gemcitabine

Friebel TM, Domchek SM, Rebbeck TR
Modifiers of cancer risk in BRCA1 and BRCA2 mutation carriers: systematic review and meta-analysis.
J Natl Cancer Inst. 2014; 106(6):dju091 [PubMed] Article available free on PMC after 01/06/2015 Related Publications
BACKGROUND: There is substantial variability in cancer risk in women who have inherited a BRCA1 or BRCA2 (BRCA1/2) mutation. Numerous factors have been hypothesized to modify these risks, but studies are of variable quality, and it remains unclear which of these may be of value in clinical risk assessment.
METHODS: PubMed and Web of Science databases were searched for articles published through September 2013. Fixed effects meta-analysis was done using the hazard ratios and/or odds ratios to estimate the pooled effect estimates (ES) and 95% confidence intervals (CIs) to identify factors that are associated with cancer risk modification in BRCA1/2 mutation carriers.
RESULTS: We identified 44 nonoverlapping studies that met predefined quality criteria. Sufficient evidence is available to make clinically relevant inferences about a number of cancer risk modifiers. The only variable examined that produced a probable association was late age at first live birth, a meta-analysis showed a decrease in the risk of breast cancer in BRCA1 mutation carriers with women aged 30 years or older vs. women younger than 30 years (ES = 0.65; 95% CI =0.42 to 0.99). The same was shown for women aged 25 to 29 years versus those aged less than 25 years (ES = 0.69; 95% CI = 0.48 to 0.99). Breastfeeding and tubal ligation were associated with reduced ovarian cancer risk in BRCA1 mutation carriers; oral contraceptives were associated with reduced risk among BRCA1/2 mutation carriers. Smoking was associated with increased breast cancer risk in BRCA2 mutation carriers only.
CONCLUSIONS: Data assessing many potential risk modifiers are inadequate, and many have not been externally validated. Although additional studies are required to confirm some associations, sufficient information is available for some risk factors to be used in risk counseling or lifestyle modification to minimize cancer risk in BRCA1/2 mutation carriers

Related: Ovarian Cancer

Rabban JT, Garg K, Crawford B, et al.
Early detection of high-grade tubal serous carcinoma in women at low risk for hereditary breast and ovarian cancer syndrome by systematic examination of fallopian tubes incidentally removed during benign surgery.
Am J Surg Pathol. 2014; 38(6):729-42 [PubMed] Related Publications
Early detection of sporadic pelvic serous carcinoma remains an elusive goal. In women at high risk for hereditary breast and ovarian cancer syndrome who undergo prophylactic salpingectomy, systematic pathologic examination of the fallopian tubes will detect occult tubal cancer, mostly in the fimbriae, of a minority of women. Such tubal cancers are the putative precursor to advanced-stage pelvic cancer. We hypothesized that early tubal cancer detection can also be accomplished in women at low risk using a similar approach. In this study, we performed complete and systematic examination of the fallopian tubes removed during surgery performed for benign indications. Among 522 women, 4 cases of serous tubal intraepithelial carcinoma (STIC) were identified. Three of these cases would have gone undetected using the current standard of care of sampling only a single random section of the tube. The fourth case was accompanied by occult ovarian carcinoma. The fimbriae contained STIC in 3 of the 4 cases and atypical mucosa in 1 case in which the STIC was in the nonfimbriated portion of the tube. The morphologic and immunohistochemical features (aberrant p53 and MIB-1) of these STICs were similar to those expected in high-risk women. All 4 patients with STIC underwent BRCA1 and BRCA2 gene testing; no germline mutations were identified in any patient. An additional 11 specimens contained atypical mucosal proliferations that fell short of morphologic and immunohistochemical criteria for STIC. Two of these 11 fulfilled criteria for a serous tubal intraepithelial lesion, and the remaining atypical proliferations exhibited normal p53 and MIB-1. For most specimens, the fimbriae could be completely submitted in 1 or 2 cassettes per tube. These results demonstrate that systematic examination of the tubal fimbriae can serve as a form of early detection of sporadic tubal cancer without incurring significant labor or cost. We propose that the tubal fimbriae should be completely examined in all patients undergoing benign surgery even if there are no clinical features to suggest risk for hereditary breast and ovarian cancer syndrome.

Related: Cancer Screening and Early Detection Fallopian Tube Cancer MKI67 TP53

Pettersson A, Graff RE, Ursin G, et al.
Mammographic density phenotypes and risk of breast cancer: a meta-analysis.
J Natl Cancer Inst. 2014; 106(5) [PubMed] Related Publications
BACKGROUND: Fibroglandular breast tissue appears dense on mammogram, whereas fat appears nondense. It is unclear whether absolute or percentage dense area more strongly predicts breast cancer risk and whether absolute nondense area is independently associated with risk.
METHODS: We conducted a meta-analysis of 13 case-control studies providing results from logistic regressions for associations between one standard deviation (SD) increments in mammographic density phenotypes and breast cancer risk. We used random-effects models to calculate pooled odds ratios and 95% confidence intervals (CIs). All tests were two-sided with P less than .05 considered to be statistically significant.
RESULTS: Among premenopausal women (n = 1776 case patients; n = 2834 control subjects), summary odds ratios were 1.37 (95% CI = 1.29 to 1.47) for absolute dense area, 0.78 (95% CI = 0.71 to 0.86) for absolute nondense area, and 1.52 (95% CI = 1.39 to 1.66) for percentage dense area when pooling estimates adjusted for age, body mass index, and parity. Corresponding odds ratios among postmenopausal women (n = 6643 case patients; n = 11187 control subjects) were 1.38 (95% CI = 1.31 to 1.44), 0.79 (95% CI = 0.73 to 0.85), and 1.53 (95% CI = 1.44 to 1.64). After additional adjustment for absolute dense area, associations between absolute nondense area and breast cancer became attenuated or null in several studies and summary odds ratios became 0.82 (95% CI = 0.71 to 0.94; P heterogeneity = .02) for premenopausal and 0.85 (95% CI = 0.75 to 0.96; P heterogeneity < .01) for postmenopausal women.
CONCLUSIONS: The results suggest that percentage dense area is a stronger breast cancer risk factor than absolute dense area. Absolute nondense area was inversely associated with breast cancer risk, but it is unclear whether the association is independent of absolute dense area.

Palena C, Roselli M, Litzinger MT, et al.
Overexpression of the EMT driver brachyury in breast carcinomas: association with poor prognosis.
J Natl Cancer Inst. 2014; 106(5) [PubMed] Related Publications
BACKGROUND: The epithelial-mesenchymal transition (EMT) has been implicated as an important process in tumor cell invasion, metastasis, and drug resistance. The transcription factor brachyury has recently been described as a driver of EMT of human carcinoma cells.
METHODS: Brachyury mRNA and protein expression was analyzed in human breast carcinomas and benign tissues. The role of brachyury in breast tumor prognosis and drug resistance and the ability of brachyury-specific T cells to lyse human breast carcinoma cells were also evaluated. Kaplan-Meier analyses were used to evaluate the association between brachyury expression and survival. All statistical tests were two-sided.
RESULTS: The level of brachyury expression in breast cancer cells was positively associated with their ability to invade the extracellular matrix, efficiently form mammospheres in vitro, and resist the cytotoxic effect of docetaxel. A comparison of survival among breast cancer patients treated with tamoxifen in the adjuvant setting who had tumors with high vs low brachyury mRNA expression demonstrated that high expression of brachyury is associated as an independent variable with higher risk of recurrence (hazard ratio [HR] = 7.5; 95% confidence interval [CI] = 2.4 to 23.5; P = 5.14×10(-4)) and distant metastasis (HR = 15.2; 95% CI = 3.5 to 66.3; P = 3.01×10(-4)). We also demonstrated that brachyury-specific T cells can lyse human breast carcinoma cells.
CONCLUSIONS: The studies reported here provide the rationale for the use of a vaccine targeting brachyury for the therapy of human breast cancer, either as a monotherapy or in combination therapies.

Topps A, Clay V, Absar M, et al.
The sensitivity of pre-operative axillary staging in breast cancer: comparison of invasive lobular and ductal carcinoma.
Eur J Surg Oncol. 2014; 40(7):813-7 [PubMed] Related Publications
INTRODUCTION: Axillary ultrasound (AUS) with fine-needle aspiration (FNA) biopsy of abnormal lymph nodes is important for pre-operative staging and planning the surgical management of the axilla. Invasive lobular carcinoma (ILC) metastases are thought to be difficult to detect because the cells are small and on cytology resemble lymphocytes. To investigate this we directly compared the sensitivity of pre-operative axillary staging between ILC and invasive ductal carcinoma (IDC).
METHOD: Consecutive patients that presented in a single breast unit with pure IDC between April 2005 and December 2006 and pure ILC between January 2008 and December 2012 were retrospectively identified from pathology records. Pre-operative axillary ultrasound and FNA biopsy results were compared with post-operative histopathology from the sentinel node biopsy (SNB) or axillary lymph node dissection (ALND).
RESULTS: A total of 275 and 142 axillae were identified in the IDC and ILC groups respectively. In the node positive patients there was no significant difference in the sensitivity of AUS (IDC vs. ILC; 58.7% vs. 52.8%). However, there was a significant difference in the sensitivity of ultrasound-guided FNA biopsy of abnormal nodes (IDC vs. ILC; 98.4% vs. 53.6%; p < 0.001).
CONCLUSION: AUS has comparative sensitivities between IDC and ILC populations. In contrast, FNA biopsy of abnormal axillary nodes is clearly less sensitive in the ILC group. In these patients, who have abnormal AUS, we suggest that a core biopsy is required to improve the pre-operative staging and prevent unnecessary surgical procedures.

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