The Breast

Accuracy of telomerase in estimating breast cancer risk: A systematic review and meta-analysis

2011-09-12

Abstract: Objective: To determine the accuracy of telomerase activity in predicting a higher risk for breast cancer.Study design: A quantitative systematic review was performed. Studies that detected telomerase activities in breast tissue were included.Results: Twenty-five primary studies were analyzed, which included 2395 breast lesions. The proportion of breast cancer was 60.8%. Eighty-two percent (1193/1455) of breast cancer cases and 18% (169/940) of benign lesions cases were positive for telomerase activity. For breast cancer vs benign or normal breast tissue, the pooled likelihood ratio for the presence of telomerase activity was 4.5 (95% confidence interval [CI], 3.1–6.5) and the post-test probability was 88% (95% CI, 83–91). For breast cancer vs benign or normal tissue, the area under the summary receiver operating characteristic (SROC) curve was 0.89 with the Q* point value of 0.82.Conclusion: Our systematic review showed that telomerase activity was significantly present in breast cancer when compared with normal breast tissue or benign breast lesions.

Bone health management in patients with breast cancer: Current standards and emerging strategies

Matti S. Aapro, Robert E. Coleman — 2011-09-28

Abstract: In women who develop bone metastases from breast cancer (BC), interactions between tumor cells and osteoclasts within the bone lead to localized bone destruction and increase the risk of skeletal-related events (SREs). Bisphosphonates inhibit osteoclast-mediated bone resorption, and have been used extensively for treating post-menopausal osteoporosis and reducing the risk of SREs in patients with bone metastases. A number of clinical trials in women with early stage BC have demonstrated that adding bisphosphonates to adjuvant endocrine therapy can prevent bone loss and may prevent disease recurrence and improve disease-free survival. In women with bone metastases from BC, bisphosphonates have demonstrated efficacy for reducing skeletal morbidity and pain and improving quality of life. Recent economic analyses have demonstrated that bisphosphonate therapy is a cost-effective use of healthcare resources. This review summarizes the available data for bisphosphonate benefits in both the adjuvant and metastatic settings in the context of evolving clinical practice.

Triple negative breast cancer: Proposals for a pragmatic definition and implications for patient management and trial design

2011-10-10

Abstract: In trials in triple negative breast cancer (TNBC), oestrogen and progesterone receptor negativity should be defined as < 1% positive cells. Negativity is a ratio of <2 between Her2 gene copy number and centromere of chromosome 17 or a copy number of 4 or less. In routine practice, immunohistochemistry is acceptable given stringent quality assurance. Triple negativity emerging after neoadjuvant treatment differs from primary TN and such patients should not enter TNBC trials. Patients relapsing with TN metastases should be eligible even if their primary was positive. Rare TN subtypes such as apocrine, adenoid-cystic and low-grade metaplastic tumours should be excluded. TN and basal-like (BL) signatures overlap but are not equivalent. Since the significance of basal cytokeratin or EGFR overexpression is not known and we lack validated assays, these features should not be used to subclassify TN tumours. Tissue collection in trials is mandatory so the effect on outcome of different tumour phenotypes and BRCA mutation can be explored. No prospective studies have established that TN tumours have particular sensitivity or resistance to any specific chemotherapy agent or radiation. TNBC patients should be treated according to tumour and clinical characteristics.

Higher efficacy of letrozole in combination with trastuzumab compared to letrozole monotherapy as first-line treatment in patients with HER2-positive, hormone-receptor-positive metastatic breast cancer – Results of the eLEcTRA trial

2011-08-22

Abstract: The eLEcTRA trial compared efficacy and safety of letrozole combined with trastuzumab to letrozole alone in patients with HER2 and hormone receptor (HR) positive metastatic breast cancer (MBC). Patients were randomized to either letrozole alone (arm A, n = 31) or letrozole plus trastuzumab (arm B, n = 26) as first-line treatment. Additional 35 patients with HER2 negative and HR positive tumors received letrozole alone (arm C).Median time to progression in arm A was 3.3 months compared to 14.1 months in arm B (hazard ratio 0.67; p = 0.23) and 15.2 months in arm C (hazard ratio 0.71; p = 0.03). Clinical benefit rate was 39% for arm A compared to 65% in arm B (odds ratio 2.99, 95% CI 1.01–8.84) and 77% in arm C (odds ratio 5.34, 95% CI 1.83–15.58).The eLEcTRA trial showed that the combination of letrozole and trastuzumab is a safe and effective treatment option for patients with HER2 positive and HR positive MBC.

Comparative study of spatial localization of HER-2 and CEP17 signals and of HER-2/CEP17 ratios, in “thin” and “thick” tissue sections

E. Kouvaras, C.N. Papandreou, D.D. Daliani, A. Athanasiadis, G.K. Koukoulis — 2011-08-22

Abstract: One presumed drawback of performing fluorescence in situ hybridization on routine tissue sections for HER-2 status evaluation in breast carcinomas is nuclear truncation. Therefore, HER-2/CEP 17 ratios were compared in routine (4 μm) vs. thicker (15 μm) tissue sections. Additionally, the distances of both signals from the nuclear center were measured by three-dimensional image analysis. HER-2 and CEP 17 signals’ number increased in thick sections; however, HER-2/CEP 17 ratios were decreased. This could be attributed to a preferential increase in CEP17 signals explained by their more peripheral localization and apparent "loss" in truncated nuclei. The aforementioned decrease of HER-2 ratios did not alter HER-2 status except in cases in the equivocal category where it changed from equivocal to non-amplified. Thus, at least a subset of the equivocal cases could represent an artifactual increase of HER-2 ratio related to nuclear truncation and loss of peripheral CEP 17 signals in routine sections.

Relationship between body mass index and preoperative treatment response to aromatase inhibitor exemestane in postmenopausal patients with primary breast cancer

2011-08-22

Abstract: Background: Some studies have shown that high body mass index (BMI) is associated with inferior outcome after adjuvant therapy with anastrozole in breast cancer patients. We aimed to investigate predictive effect of BMI on clinical response to neoadjuvant therapy with exemestane in postmenopausal patients with primary breast cancer.Patients and methods: The study group consisted of 109 patients from the JFMC 34-0601 neoadjuvant endocrine therapy trial. Patients were categorized into three groups according to BMI: low (BMI < 22 kg/m2), intermediate (22 ≤ BMI < 25 kg/m2) and high (BMI ≥ 25 kg/m2). Statistical analyses were performed to explore the predictive effect of BMI on clinical response.Results: Higher BMI correlated with positive progesterone receptor status (p < 0.01) and low Ki-67 index (p = 0.03). Objective response rates (ORR) were 21.7% in low BMI, 56.0% in intermediate BMI and 60.6% in high BMI, respectively (p = 0.01). In a multivariate analysis, low BMI was an independent negative predictor of clinical response.Conclusion: Low BMI was associated with a decreased ORR to neoadjuvant endocrine therapy with exemestane. Our results may suggest that the predictive effect of BMI varies according to the type of aromatase inhibitor and objective outcome.

Persistent pain after targeted intraoperative radiotherapy (TARGIT) or external breast radiotherapy for breast cancer: A randomized trial

2011-08-24

Abstract: Persistent pain after breast cancer treatment (PPBCT) affects between 25 and 60% of patients depending on surgical and adjuvant treatment. External breast radiotherapy (EBRT) has been shown to be a riskfactor for PPBCT, raising the question whether intraoperative radiation therapy (IORT), with its smaller radiation field may reduce the development of PPBCT. Using data from the TARGIT-A trial, the aim of this study was to compare these two treatments with regard to development of PPBCT.A total of 281 patients enrolled in the TARGIT-A trial from the Copenhagen University Hospitals was screened for participation, and a total of 244 patients were included and received a detailed questionnaire. The response rate was 98%, leaving 238 patients for the final analysis.Pain prevalence were 33.9% in the EBRT group and 24.6% in the IORT group (p = 0.11). Treatment with IORT may not alter the risk of PPBCT.

Characteristics and outcomes according to molecular subtypes of breast cancer as classified by a panel of four biomarkers using immunohistochemistry

2011-08-25

Abstract: To investigate the significance of immunohistochemical molecular subtyping, we evaluated outcomes of subtypes based on estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67. Using tissue microarrays, 1006 breast cancer patients between November 1999 and August 2005 were categorized into four subtypes: luminal A (ER+ and/or PR+, HER2-, Ki-67 < 14%), luminal B (ER+ and/or PR+, HER2-, Ki-67 ≥ 14% or ER+ and/or PR+, HER2+), HER2-enriched (ER-, PR-, HER2+), and triple-negative breast cancer (TNBC) (ER-, PR-, HER2-). Demographics, recurrence patterns, and survival were retrospectively analyzed using uni-/multivariate analyses. Luminal A, luminal B, HER2-enriched, and TNBC accounted for 53.1%, 21.7%, 9.0%, and 16.2% of cases, respectively. Luminal A presented well-differentiation and more co-expression of hormone receptors comparing to luminal B. HER2-enriched showed larger size and higher nodal metastasis. TNBC demonstrated younger age at diagnosis, larger size, undifferentiation, higher proliferation, and frequent visceral metastases. The peak of recurrence for luminal A was at 36 months postoperatively, while that for HER2-enriched and TNBC peaked at 12 months. The relapse risk of luminal B was mixed. Luminal A showed the best survival, but no difference was observed between the other three subtypes. When matched by nodal status, however, TNBC showed the worst outcomes in node-positive patients. In multivariate analyses, luminal A remained a positive prognostic significance. Immunohistochemically-defined subtypes showed different features, recurrence patterns, and survival. Therefore, molecular subtypes using four biomarkers could provide clinically useful information of tumor biology and clinical behaviors, and could be used for determining treatment and surveillance strategies.

Re-evaluating the role of axillary lymph node dissection in screen-detected breast cancer patients

M. Barry, M.R. Kell — 2011-09-07

Abstract: Introduction: The American College of Surgeons Oncology Group (ACOSOG), Z0011 trial, demonstrated that there was no therapeutic benefit from completion lymphadenectomy in early stage breast cancer patients with positive sentinel node (SLN) biopsy. Patients with asymptomatic screen-detected tumors may represent a subgroup where completion axillary dissection with its attendant morbidities is unacceptable. Therefore, the aim of this study was to evaluate the role of ALND in an asymptomatic screen-detected breast cancer cohort.Methods: Patients were recruited from the national screening program which offers women (aged 50 to 65) biannual digital mammography. Over a 1 year period 519 screen-detected breast cancer patients were recruited of which 110 had a positive SLN.Results: Of 519 patients in a national screening program that were clinically/radiologically identified as axillary node negative, 110 (21.2%) had a positive SLN. All 110 (T1 = 68, T2 = 42) patients proceeded to have an axillary clearance. 68 (59%) had T1 tumors and of these 40 (60%), despite a positive SLN, had no metastatic nodes on final pathological analysis of their axilla. In addition, 21 (50%) patients with T2 tumors had no metastatic nodes except for a positive SNB. Furthermore, only 6 (8.8%) of T1 tumors with a positive SLN had 4 or more metastatic axillary lymph nodes.Conclusion: 55.45% of patients with a screen-detected T1/T2 tumor had negative completion lymphadectomy. These findings compel us to re-evaluate the role of axillary dissection in the screen-detected asymptomatic breast cancer population to avoid unnecessary ALND with its attendant morbidities.

Objective assessment of aesthetic outcome after breast conserving therapy: Subjective third party panel rating and objective BCCT.core software evaluation

2011-08-18

Abstract: We analysed intra- and inter-rater agreement of subjective third party assessment and agreement with a semi-automated objective software evaluation tool (BCCT.core).We presented standardized photographs of 50 patients, taken shortly and one year after surgery to a panel of five breast surgeons, six breast nurses, seven members of a breast cancer support group, five medical and seven non-medical students. In two turns they rated aesthetic outcome on a four point scale. Moreover the same photographs were evaluated by the BCCT.core software.Intra-rater agreement in the panel members was moderate to substantial (k = 0.4–0.5; wk = 0.6–0.7; according to different subgroups and times of assessment). In contrast inter-rater agreement was only slight to fair (mk = 0.1–0.3). Agreement between the panel participants and the software was fair (wk = 0.24–0.45).Subjective third party assessment only fairly agree with objective BCCT.core evaluation just as third party participants do not agree well among each other.

Imaging sensitivity of dedicated positron emission mammography in relation to tumor size

2011-08-29

Abstract: Positron emission mammography (PEM) has been reported to have higher sensitivity than whole-body positron emission tomography (PET)due to higher spatial resolution. However, no direct evidence exists regarding the imaging sensitivity of PEM related to lesion size. In the present study, imaging sensitivity of PEM was investigated in relation to pathologically confirmed tumor size.A total of 113 breast lesions from 101 patients were included in the analysis. The patients underwent 18F-fluorodeoxyglucose (FDG) PEM and whole-body PET/computed tomography (CT) before surgical resection, and images were analyzed visually and quantitatively using the tumor-to-normal-tissue uptake ratio (TNR). Tumors were classified into four groups based on size using pathologic results, and sensitivities of PEM and PET/CT were compared in the overall subjects and in each size group.In visual analysis, PEM showed significantly higher imaging sensitivity than PET/CT (95% vs. 87%; P = 0.004), which was more definite in the small-tumor groups. In quantitative analysis, the TNR of PEM was significantly higher than that of PET/CT in the small-tumor groups, whereas no difference was found in the overall group. With a cutoff TNR of 2.5, PEM showed significantly higher sensitivity than PET/CT in the overall and small-tumor groups.In conclusion, PEM had higher imaging sensitivity than PET/CT, particularly in small tumors. The results suggest that PEM may be used for diagnosis and characterization of small lesions as a supplementary imaging modality for PET/CT.

A pilot study to examine the experiences and attitudes of women with breast cancer towards one versus two-step axillary surgery

V. Jenkins, H. Harder, M. Babar, S. Merry, S. Newbury, M. Kissin, C. Zammit — 2011-08-29

Abstract: Purpose: To elicit the views, experiences and preferences of women with clinically node negative breast cancer towards intra-operative sentinel lymph node biopsy (SLNB) analysis.Methods: Focus groups with 14 women with breast cancer from two UK centres; one group had undergone the standard practice of waiting two weeks for results of their axillary surgery, the other had experienced the intra-operative SLNB analysis.Results: Women generally were unaware about their lymph nodes, what their function is and how they are removed. Preference was indicated for intra-operative sentinel lymph node biopsy (SLNB) analysis provided clear descriptions were given about the risk of experiencing false negative and false positive results.Discussion: Adopting an intra-operative analysis technique of axillary nodes was viewed as an excellent option by women from both centres. The immediacy of knowing the results was seen as a great advantage for their physical and psychological well being and more cost effective.

The decline in breast cancer mortality in Europe: An update (to 2009)

2011-09-09

Abstract: We updated trends in breast cancer mortality in Europe up to the late 2000’s. In the EU, age-adjusted (world standard population) breast cancer mortality rates declined by 6.9% between 2002 and 2006, from 17.9 to 16.7/100,000. The largest falls were in northern European countries, but more recent declines were also observed in central and eastern Europe. In 2007, all major European countries had overall breast cancer rates between 15 and 19/100,000. In relative terms, the declines in mortality were larger at younger age (−11.6% at age 20–49 years between 2002 and 2007 in the EU), and became smaller with advancing age (−6.6% at age 50–69, −5.0% at age 70–79 years). The present report confirms and further quantifies the persisting steady fall in breast cancer mortality in Europe over the last 25–30 years, which is mainly due to advancements in the therapy.

Anxiety after an abnormal screening mammogram is a serious problem

2011-09-19

Abstract: Purpose: The aim of this study was to analyze the possible negative psychological consequences of a false positive screening mammogram (FPSM). We compared anxiety evoked by first (FSM) versus repeat screening mammogram (RSM). Questionnaires were completed prior to the diagnosis and during follow up.Results: No differences in anxiety, depressive symptoms, and Quality of Life (QoL) were found between FSM (N = 186) or RSM (N = 296) groups. All women experienced high anxiety before diagnosis was known. High trait anxiety was predictive for more anxiety, depressive symptoms, and lower QoL. Women with low score on trait anxiety were more momentary anxious in FSM group compared with RSM group (p = 0.048).Conclusion: Negative psychological consequences after an FPSM are seen in all women. These effects are strengthened by personality and timing of the screening mammogram.All women should receive correct information concerning the negative psychological effects and should be offered psychosocial support if needed.

Ixabepilone plus capecitabine in advanced breast cancer patients with early relapse after adjuvant anthracyclines and taxanes: A pooled subset analysis of two phase III studies

2011-09-22

Abstract: Background: Metastatic breast cancer (MBC) patients with rapid disease relapse after neo/adjuvant chemotherapy including anthracyclines and taxanes have limited treatment options and their efficacy is marginal. Two phase III studies compared ixabepilone plus capecitabine vs. capecitabine alone as first-line treatment in MBC patients pretreated with anthracyclines and taxanes in the neo/adjuvant setting. Here we report the efficacy and safety of these treatments in a prespecified subset of patients whose disease relapsed within 12 months.Patients and methods: Of 1973 patients across two studies, 293 relapsed within 12 months of neo/adjuvant treatment and received ixabepilone plus capecitabine (n = 149) or capecitabine alone (n = 144) as first-line chemotherapy for MBC. Analysis included progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and toxicity.Results: In 293 patients, ixabepilone plus capecitabine, as compared to capecitabine alone, increased PFS (median: 5.6 months vs. 2.8 months; hazard ratio, 0.58; p < 0.0001), ORR (46% vs. 24%) and OS (median: 15.1 months vs. 12.5 months; hazard ratio, 0.84; p = 0.208). Major toxicities of this regimen included neuropathy, neutropenia and hand-foot syndrome, but were manageable.Conclusions: Patients with breast cancer with early relapse following neo/adjuvant treatment with anthracyclines and taxanes may benefit from ixabepilone plus capecitabine. (ClinicalTrials.gov identifiers: NCT00080301 and NCT00082433.)

Bone health in a prospective cohort of postmenopausal women receiving aromatase inhibitors for early breast cancer

2011-09-19

Abstract: Objective: Baseline bone health in postmenopausal women is poorly characterized in prospective series of early breast cancer (EBC) patients candidates to aromatase inhibitor (AI) therapy. Our objective is to comprehensively evaluate bone health in a prospective clinical cohort of patients recruited prior to adjuvant AI therapy, with the aim of establishing potential AI impact on bone loss and fractures.Methods: From January 2006 to April 2010, we consecutively included 343 women with EBC who were about to start adjuvant AI therapy. Participants were assessed at baseline (before AI initiation) and at 3 months, with annual assessments thereafter. Bone mineral density (BMD), spine X-ray, bone metabolism (vitamin D [25(OH)D], bone turnover markers [BTM]), arthralgia and quality of life are measured.Results: Mean age was 61.9 years; 197 (57.4%) had been previously treated with tamoxifen; 145 (42.3%) were taking exemestane, 187 (54.5%) letrozole, and 11 (3.2%) anastrozole.Analysis of baseline data shows only 59 women (17.7%) had normal BMD; 200 (60.1%) had osteopenia and 74 (22.2%) had osteoporosis; 39 women (11.4%) had a prevalent fracture, 293 (89.1%) had 25(OH)D insufficiency (<30 ng/ml), and 61 (18.5%) severe deficiency (<10 ng/ml). Low 25(OH)D concentrations were associated with lower BMD and 233 (67.9%) participants had some degree of arthralgia.Conclusions: Low bone mass, prevalent fractures and vitamin D insufficiency were highly prevalent among candidates to adjuvant AI for EBC. Therefore, it is crucial to assess BMD, prevalent fractures and 25(OH)D concentrations before starting AI therapy and during follow-up.

Breast implant related Anaplastic Large Cell Lymphoma presenting as late onset peri-implant effusion

Trevor J. Smith, Reena Ramsaroop — 2011-08-16

Abstract: In the past 10 years there has been a number of case reports of lymphoma associated with implants. In January 2011 the US FDA (United States Food and Drug Administration) produced a review of the medical literature reporting an association between breast implants and Anaplastic Large Cell Lymphoma (ALCL). A common presenting feature is late onset effusion around the implant. We report the first case in New Zealand and add to the worldwide total of 34 reported cases.

Breast reconstruction: A quality measure for breast cancer care?

2011-09-05

Abstract: Parallel to its life-threatening nature, breast cancer can affect physical integrity, having a psychosocial impact on patients. Determining the optimal proportion of patients who should undergo breast reconstruction after cancer surgery represents a complex task. What seems to be unquestionable is that the ability to offer reconstruction and a wide range of surgical options plays an important role in current breast cancer management. The multidisciplinary approach is a paramount aspect not only for a successful oncologic treatment, but also for improving patient quality of life.

Can all beta blockers improve the breast cancer survival?

Mehmet Ali Nahit Sendur, Sercan Aksoy, Sebnem Yaman, Zafer Arik, Kadri Altundag — 2011-10-17

Recent studies have showed the importance of neuroendocrine regulation of breast cancer progression. Preclinical and epidemiological studies have designated that sympathetic nervous system and adrenergic neurotransmitters such as epinephrine and neuroepinephrine can regulate several pathways for tumor progression and metastasis. Emerging data suggest a dramatic new role for β-blockers in the treatment of breast cancer. However, there is limited data about the association of breast cancer and with a selective metoprolol usage. Thus, we aimed to investigate relationship between metoprolol usage and clinico-pathological properties of breast cancer.

Men’s experiences of gynaecomastia and corrective surgery: A qualitative report

Sinead NiMhurchadha, Jennifer Hughes, Charles Nduka, Diana Harcourt — 2011-11-09

An increasing number of men are reporting dissatisfaction with some aspect of their body. It is therefore unsurprising that the number of men undergoing breast reduction surgery in the UK increased by 80% from 2008–2009 and a further 28% increase has been reported from 2009–2010. Given this stark increase, this study wished to understand the main reasons that men with gynaecomastia undergo reduction surgery and their experiences of surgery.

Letter in response to Macdonald C, Nakhdjevani A, Shah A. The “Swiss-Roll” flap: A modified C–V flap for nipple reconstruction. The Breast 20 (2011) 475–477

Edward Matthews, Foiz Ahmed, John Breeze, Simon Heppell — 2011-12-14

We write in response to the recent article by Macdonald et al. advocating a method of local flap nipple reconstruction . Nipple-areolar complex (NAC) reconstruction is the final phase of breast reconstruction and therefore importance is put upon the creation of a matching NAC for the reconstructed breast. This has inherent challenges to the surgery and a multitude of variations on the C–V flap are reported. We feel the senior author’s technique, termed the “cigar-roll” offers a simpler design and confers advantage in both procedure and morphology of the neo-complex . There is less tissue loss from the breast as the apices of the wings are not discarded, this also allows for a shorter transverse scar. Giving the advantage of a reduced donor site wound which becomes more pertinent when matching to the contra-lateral NAC, as the scar can be maintained within the tattooed neo-areola.