The Breast

Editorial

Alberto Costa — 2011-11-07

For more than one hundred years cancer was considered an external entity growing into the body and acting against it. The approach to treatment was: seek and destroy. Aggressive surgery, heavy radiotherapy, intensive chemotherapy were the norm. We now know that cancer cells result from genetic changes to normal cells, and we now try to ‘cure’ them without causing too much damage to healthy cells. Consequently, surgery has become more and more conservative.

Evaluation of the evidence on staging imaging for detection of asymptomatic distant metastases in newly diagnosed breast cancer

M.E. Brennan, N. Houssami — 2011-11-17

Abstract: While guidelines recommend against routine use of staging imaging to detect asymptomatic distant metastases (DM) in newly diagnosed breast cancer (BC), modern imaging technologies may have improved detection capability and may have a role in some cases. We performed a systematic review of studies (1995–2011) evaluating the prevalence of DM and the accuracy of staging imaging for detection of asymptomatic DM. Twenty-two studies reporting on 14,824 BC subjects (median age 53 years) undergoing staging imaging were eligible. Median prevalence of DM was 7.0% (range 1.2–48.8%); prevalence increased with increasing BC stage. Conventional imaging studies had lower DM prevalence than studies of PET(PET/CT). Imaging median sensitivity/specificity respectively were: combined conventional imaging 78.0%/91.4%; bone scintigraphy 98.0%/93.5%; chest X-ray 100%/97.9%; liver ultrasound 100%/96.7%; CT chest/abdomen 100%/93.1%; FDG-PET 100.0%/96.5%; FDG-PET/CT 100%/98.1%. Low prevalence of DM was seen in Stage I–II BC with much higher prevalence in more advanced disease. Accuracy of PET modalities was very high however the high proportion of detected asymptomatic DM partly reflects selection bias.

Clinical review – Breast adenoid cystic carcinoma

2011-12-12

Abstract: Objectives: To review the published literature on the diagnosis and management of adenoid cystic carcinoma (ACC) of the breast.Materials and Methods: Papers were identified by searching PubMed using the terms « adenoid cystic carcinoma » and « breast ». Additional papers were identified by reviewing references of relevant articles.Results: ACC of the breast is a rare tumour comprising less than 0.1% of breast malignancies. Its cellular origin in the breast remains unclear. The histological characteristics of ACC in the breast are similar to those of ACC of the salivary glands. However the prognosis of ACC of the breast is better than that of other localizations with prolonged survival. Breast-conserving treatment including postoperative radiotherapy seems to be equivalent to mastectomy alone with respect to survival. The value of adjuvant systemic therapies is not established. Late relapses can occur, so long-term follow-up is mandatory for these patients.Conclusions: ACC of the breast has a favourable prognosis. An accurate diagnosis and appropriate treatment are therefore important.

A critical review of women's sleep–wake patterns in the context of neo-/adjuvant chemotherapy for early-stage breast cancer

Grigorios Kotronoulas, Yvonne Wengström, Nora Kearney — 2011-12-22

Abstract: Complaints of poor nocturnal sleep and daytime dysfunction may be frequent among women receiving chemotherapy for breast cancer. A critical review of the literature was conducted, which aimed at summarising and critically analysing findings regarding sleep in women with early-stage breast cancer across neo-/adjuvant chemotherapy treatment. A systematic search of three electronic databases (Medline, CINAHL, EMBASE) was conducted from January 1980 to July 2011. Twenty-one articles reporting on 12 studies were included for analysis based on pre-specified selection criteria. Varying deficits in sleep parameters may be evident in a significant part of this population. Yet, research data are not equally distributed among the different sleep components, or across all major time points throughout chemotherapy. More systematic investigation of the experience of disrupted sleep in this population with longitudinal mixed-methods studies is warranted to ensure that person-tailored and clinically meaningful care is delivered.

Epirubicin: Is it like doxorubicin in breast cancer? A clinical review

Mustafa Khasraw, Richard Bell, Chau Dang — 2012-01-19

Abstract: Anthracyclines are among the most effective chemotherapy treatments available for various types of cancer. The anthracyclines commonly used in treatment of breast cancer are either epirubicin or doxorubicin. Epirubicin is an epimer of doxorubicin with important role in the chemotherapy treatment of both early and metastatic breast cancer. The efficacy of epirubicin is similar to doxorubicin while epirubicin has a different toxicity profile particularly in regard to cardiotoxicity. Epirubicin has been incorporated into most of the anthracycline containing chemotherapy combinations in well-conducted clinical trials involving large numbers of patients. It has also been investigated in studies involving the administration of epirubicin in dose-dense chemotherapy schedules. Short term follow up of dose-dense clinical trials demonstrated safety comparable to that of doxorubicin. This review summarizes published clinical trials investigating epirubicin in the treatment of early and advanced breast cancer.

Use of Pre-operative MRI in DCIS of the breast

M. Puttick, A. Doyle, A. Ng, W. Jones, I. Cranshaw — 2012-04-01

Background and Purpose: Most DCIS is diagnosed on a screening mammogram, but this can underestimate the extent of DCIS. Breast MRI is a more sensitive imaging technique than mammography. The aim of this study was to evaluate whether a pre-operative MRI would more accurately gauge the extent of disease within a breast, thereby informing surgical decision making.

Risk of additional axillary metastases after micrometastases in sentinel lymph node in a Western Australian population

H. Ballal, R. Kamyab, B. Wood, A. Yeo, F. Abdul Aziz — 2012-04-01

Background and Purpose: The presence of micrometastases in sentinel nodes (SN) in patients with early breast cancer has been shown to be associated with a poorer prognosis. The management of micrometastases remains controversial and the rate of non sentinel lymph node involvement in an Australian population is difficult to ascertain from the literature.

Local recurrence rates in young women with breast cancer following breast conservation treatment and mastectomy

R. Smith, A. Matthews, R. Poon, C. Lee, E. Choo, C.R. Lewis — 2012-04-01

Background and Purpose: Breast cancer (BC) is less common in “young” women (defined as 40 years age or less), but is associated with more aggressive biological features, higher risk of local recurrence (LR) and poorer survival. Our aim was to determine if young women with operable BC treated at our centre have an unacceptable incidence of LR following breast conservation therapy (BCT) compared to mastectomy (M).

PREDICT Plus: a population-based validation of a prognostic model for early breast cancer that includes HER2

G.C. Wishart, C.D. Bajdik, E. Dicks, E. Provenzano, P.D.P. Pharoah — 2012-04-01

Background and Purpose: Predict (www.predict.nhs.uk) is an online, breast cancer prognostication and treatment benefit tool developed using UK cancer registration data. The aim was to estimate the prognostic effect of HER2 status, include it in a new version of the model (Predict+), and to compare the 10-year survival estimates from Predict+ with the original Predict model, Adjuvant! and the observed 10-year outcome from a British Columbia dataset used previously to validate Predict and Adjuvant!.

Intraoperative assessment of sentinel nodes in breast cancer by One-step Nucleic Acid Amplification (OSNA) versus imprint cytology

E.E. Elder, J. French, H. Mahajan, N. Pathmanathan, M. Bilous — 2012-04-01

Background and purpose: Sentinel node based management of the axilla has become standard of care in early breast cancer. Low-volume nodal metastatic disease is associated with poorer prognosis and increased benefit from systemic therapy. Nevertheless, the value of completion axillary clearance in micrometastatic nodal disease has recently been questioned.

Objective breast symmetry evaluation using 3-D surface imaging

2011-08-18

Abstract: This study develops an objective breast symmetry evaluation using 3-D surface imaging (Konica-Minolta V910® scanner) by superimposing the mirrored left breast over the right and objectively determining the mean 3-D contour difference between the 2 breast surfaces. 3 observers analyzed the evaluation protocol precision using 2 dummy models (n = 60), 10 test subjects (n = 300), clinically tested it on 30 patients (n = 900) and compared it to established 2-D measurements on 23 breast reconstructive patients using the BCCT.core software (n = 690). Mean 3-D evaluation precision, expressed as the coefficient of variation (VC), was 3.54 ± 0.18 for all human subjects without significant intra- and inter-observer differences (p > 0.05). The 3-D breast symmetry evaluation is observer independent, significantly more precise (p < 0.001) than the BCCT.core software (VC = 6.92 ± 0.88) and may play a part in an objective surgical outcome analysis after incorporation into clinical practice.

Radial scar without associated atypical epithelial proliferation on image-guided 14-gauge needle core biopsy: Analysis of 49 cases from a single-centre and review of the literature

2011-09-26

Abstract: The purpose of this study was to evaluate the reliability of image-guided 14-gauge needle core biopsy in the diagnosis of radial scar without associated atypical epithelial proliferation, by comparison with definitive histological diagnosis on surgical excision. The records of 8792 consecutive image-guided 14-gauge needle core biopsy of the breast performed from January 1996 to December 2009 were reviewed. Forty-nine cases of radial scar without associated atypical epithelial proliferation were identified and compared with definitive histological diagnosis on surgical excision.The definitive histological diagnosis on surgical excision confirmed the results of image-guided 14-gauge needle core biopsy in 36 of 49 cases (73.5%), in 9 cases (18.3%) radial scar was associated with atypical epithelial proliferation, while 4 cases out of 49 cases were upgraded to carcinoma (3 cases of ductal carcinoma in situ and one case of invasive lobular carcinoma), with an underestimation rate of 8.2%.A diagnosis of radial scar without associated atypical epithelial proliferation on image-guided 14-gauge needle core biopsy does not exclude a malignancy on surgical excision; consequently during the multidisciplinary discussion further assessment by surgical excision or vacuum-assisted excision, as recently reported, needs to be considered to obtain a definitive histological diagnosis.

Immunophenotyping analysis in invasive micropapillary carcinoma of the breast: Role of CD24 and CD44 isoforms expression

2011-10-24

Abstract: We analyzed immunohistochemically the expression of CD24 and spliced variants of CD44v5 and v9 in invasive micropapillary carcinoma (IMPC) of the breast that is a rather aggressive tumor characterized by alteration of cells adhesion molecules, early lymph node metastases and poor prognosis. We analyzed 31 high-grade IMPCs and compared their expression to 22 high grade (G3) invasive ductal carcinomas of the breast (IDCs). We found a higher expression of CD24 in high-grade IMPCs with a peculiar inverted apical localization, compared to IDCs, showing a strong cytoplasmic staining; normal breast tissue resulted completely negative. IMPCs showed reduced expression of CD44v5 and CD44v9 compared with IDCs, but without a statistical significant difference. This study demonstrated that IMPC represents a distinct entity of breast carcinoma with high expression of CD24 with a typical inverted apical membrane pattern and reduction of CD44 isoforms v5 and v9, compared to IDCs. These features could explain the high lymph-vascular invasion propensity and higher metastatic capability of these tumors and could be a useful tool for a future targeted therapy.

Survival of patients with bilateral versus unilateral breast cancer and impact of guideline adherent adjuvant treatment: A multi-centre cohort study of 5292 patients

2011-09-26

Abstract: This retrospective multi-centre study is focussed on recurrence free and overall survival of bilateral breast cancer (BBC) versus unilateral breast cancer (UBC). The impact of BBC on survival is stratified to guideline adherence, according to the German national S3-guideline. Another aim of the study is to identify the influence of various guideline violations in adjuvant treatment on survival of BBC patients. 229 (4.3%) patients had BBC and 5063 (95.7%) had UBC. There is a significant association between BBC/UBC and recurrence free (RFS: p < 0.001) and overall survival (OAS: p = 0.003). Only 15.7% of patients with BBC are treated 100% guideline adherent (index- + contralateral tumour). 31.0% (30.5%) were guideline adherent with respect to the index (contralateral) tumour. The outcome decreases significantly with the number of guideline violations. There was no significant difference in RFS and OAS between BBC and UBC after adjusting for tumour size, nodal status, grading and if guideline adherent treatment was applied.Conclusion: 1. Patients with BBC have primarily a worse prognosis in terms of RFS and OAS than patients with primarily UBC.2. There is a strong association between guideline adherence and RFS/OAS of patients with BBC or UBC. The outcome decreases with the number of guideline violations.3. If guideline adherent treatment was applied (for both tumours in case of BBC) there was no significant difference in RFS and OAS between BBC and UBC after adjusting for tumour size, nodal status, grading.

mTOR in breast cancer: Differential expression in triple-negative and non-triple-negative tumors

S. Walsh, L. Flanagan, C. Quinn, D. Evoy, E.W. McDermott, A. Pierce, M.J. Duffy — 2011-09-30

Abstract: Triple-negative breast cancer (TNBC) is defined by the absence of estrogen receptors (ER), progesterone receptors (PR) and overexpression of HER2. Targeted therapy is currently unavailable for this subgroup of breast cancer patients. mTOR controls cancer cell growth, survival and invasion and is thus a potential target for the treatment of patients with TNBC. Using immunohistochemistry, mTOR and p-mTOR were measured in 89 TNBCs and 99 non-TNBCs. While mTOR expression was confined to tumor cell cytoplasm, p-mTOR staining was located in the nucleus, perinuclear area and in the cytoplasm. Potentially important, was our finding that nuclear p-mTOR was found more frequently in triple-negative than non triple-negative cancers (p < 0.001). These results suggest that mTOR may play a more important role in the progression of TNBC compared to non-TNBC. Based on these findings, we conclude that mTOR may be a new target for the treatment of triple-negative breast cancer.

The use of 3D laser imaging and a new breast replica cast as a method to optimize autologous breast reconstruction after mastectomy

Uros Ahcan, Drago Bracun, Katarina Zivec, Rok Pavlic, Peter Butala — 2011-10-10

Abstract: Aesthetically pleasing and symmetrical breasts are the goal of reconstructive breast surgery. Sometimes, however, multiple procedures are needed to improve a reconstructed breast’s symmetry and appearance. In order to avoid additional corrective procedures, we have developed a new method that uses a reverse engineering technique to produce what we call a new breast replica cast (NBRC). The NBRC is a mould of the contralateral healthy breast, designed according to preoperative laser 3D images. During surgery, the mould is used to help shape the new breast. With this method, we are able to achieve breast symmetry in terms of volume, projection, contour, and position on the chest wall more accurately, more quickly, and more safely than before.

Improved sub-areolar breast tissue removal in nipple-sparing mastectomy using hydrodissection

2011-10-04

Abstract: We report on a new technique of dissection of the nipple-areola-complex (NAC) in nipple-sparing mastectomy (NSM). NACs removed due to the presence of tumor cells beneath them were histologically examined for the presence of normal breast glandular tissue. Cases were divided into cohort 1, where NACs were dissected by sharp isolation, coring the nipple, and cohort 2, where the same procedure was preceded by hydrodissection of the areola. In 20 (17.4%) cases the planned NSM was converted to skin-sparing mastectomy (SSM) because of intraoperative findings of cancer in retro-areolar tissue. Histological examination of 20 NSMs converted to SSM showed the presence of glandular tissue in 12 out of 13 cohort 1 cases (92%) and in 1 out of 7 cohort 2 cases (14%). We conclude that hydrodissection creates a subdermal plane facilitating NAC dissection and permitting a more complete removal of breast tissue in NSM. Such radicality could prove important in the treatment of breast cancer and in BRCA 1–2 mutation carriers because of its potential for reducing the risk of relapse.

Combination of two local flaps for large defects after breast conserving surgery

Jeeyeon Lee, Youngtae Bae, Werner Audretsch — 2011-10-17

Abstract: Purpose: Oncoplastic surgery is a technique for wide excision of breast cancer without compromising the natural shape of the breast. We have combined two local flaps, referred to as a ‘combined local flap’, for large defects of the breast after a partial mastectomy.Patients and methods: Twenty-one patients with breast cancer underwent a partial mastectomy with immediate reconstruction when the surgical margin was positive and further excision was required or the tumor size was larger than the pre-operative evaluation. Reconstruction was consisted of a rotational local flap and a thoraco-epigastric flap (TEF), so-called a combined local flap. The cosmetic results were self-estimated after chemotherapy and radiotherapy according to a four-point scoring system.Results: The mean age of patients was 53.3 years and the mean tumor size was 2.2 cm. The mean excised breast volume was 133.8 mm3 and the percentage of excised volume was 20.4%. The cosmetic outcomes were judged as excellent, good, and fair in 11, 8, and 2 cases, respectively.Conclusion: The combined local flap, consisting of a rotational local flap and a TEF is a useful oncoplastic technique for large defects after breast-conserving surgery.

Influence of catechol-o-methyltransferase genotype (Val158Met) on endocrine, sympathetic nervous and mucosal immune systems in breast cancer survivors

2011-10-05

Abstract: Stress can play an important role in development of cancer-related fatigue (CRF) by activating the hypothalamic-pituitary-adrenal (HPA) axis, the sympathetic nervous system (SNS), and altering the immune system. This study examined the influence of catechol-O-methyltransferase (COMT) Val158Met genotypes on salivary markers of HPA axis (cortisol), SNS (α-amylase) and immune (IgA) systems, as well as on CRF in breast cancer survivors (BCS). One-hundred BCS participated. After amplifying Val158Met COMT polymorphisms by polymerase chain reaction, three COMT genotypes were considered: Val/Val, Val/Met, Met/Met. Salivary cortisol, α-amylase activity, salivary flow rate, and IgA concentration were collected from non-stimulated saliva. CRF was assessed with the fatigue subscale of the Profile of Mood State (POMS) questionnaire. We found that BCS carrying Met/Met genotype reported higher cortisol concentration, α-amylase activity and greater CRF than those with Val/Met (P 0.20) were found. The results suggest that BCS carrying Met/Met genotype exhibit greater dysfunction of the HPA axis and SNS system associated with severe CRF. This study is important because it strives to understand biological factors that predispose some BCS to higher levels of CRF.

Non sentinel node involvement prediction for sentinel node micrometastases in breast cancer: Nomogram validation and comparison with other models

2011-10-20

Abstract: Purpose: The risk of non sentinel node (NSN) involvement varies in function of the characteristics of sentinel nodes (SN) and primary tumor. Our aim was to determine and validate a statistical tool (a nomogram) able to predict the risk of NSN involvement in case of SN micro or sub-micrometastasis of breast cancer. We have compared this monogram with other models described in the literature.Methods: We have collected data on 905 patients, then 484 other patients, to build and validate the nomogram and compare it with other published scores and nomograms.Results: Multivariate analysis conducted on the data of the first cohort allowed us to define a nomogram based on 5 criteria: the method of SN detection (immunohistochemistry or by standard coloration with HES); the ratio of positive SN out of total removed SN; the pathologic size of the tumor; the histological type; and the presence (or not) of lympho-vascular invasion.The nomogram developed here is the only one dedicated to micrometastasis and developed on the basis of two large cohorts. The results of this statistical tool in the calculation of the risk of NSN involvement is similar to those of the MSKCC (the similarly more effective nomogram according to the literature), with a lower rate of false negatives.Conclusion: this nomogram is dedicated specifically to cases of SN involvement by metastasis lower or equal to 2 mm. It could be used in clinical practice in the way to omit ALND when the risk of NSN involvement is low.

Clinical utility of routine pre-operative axillary ultrasound and fine needle aspiration cytology in patient selection for sentinel lymph node biopsy

T. Rattay, M. Muttalib, E. Khalifa, A. Duncan, S.J. Parker — 2011-10-10

Abstract: In patients with operable breast cancer, pre-operative evaluation of the axilla may be of use in the selection of appropriate axillary surgery. Pre-operative axillary ultrasound (US) and fine needle aspiration cytology (FNAC) assessments have become routine practice in many breast units, although the evidence base is still gathering. This study assessed the clinical utility of US+/−FNAC in patient selection for either axillary node clearance (ANC) or sentinel lymph node biopsy (SLNB) in patients undergoing surgery for operable breast cancer.Over a two-year period, 348 patients with a clinically negative axilla underwent axillary US. 67 patients with suspicious nodes on US also underwent FNAC. The sensitivity and specificity of axillary investigations to determine nodal involvement were 56% (confidence interval: 47–64%) and 90% (84–93%) for US alone, and 76% (61–87%) and 100% (65–100%) for FNAC combined with US, respectively. With a positive US, the post-test probability was 78%. A negative US carried a post-test probability of 25%. When FNAC was positive, the post-test probability was greater than unity. A negative FNAC yielded a post-test probability of 52%.All patients with positive FNAC and most patients with suspicious US were listed for axillary node clearance (ANC) after consideration at the multi-disciplinary team (MDT) meeting. With pre-operative axillary US+/−FNAC, 20% of patients were saved a potential second axillary procedure, facilitating a reduction in the overall re-operation rate to 12%.In this study, a positive pre-operative US+/−FNAC directs patients towards ANC. When the result is negative, other clinico-pathological factors need to be taken into account in the selection of the appropriate axillary procedure.

Breast clinic triage tool: Telephone assessment of new referrals

Leila Cusack, Meagan Brennan, Leisha Weissenberg, Katrina Moore — 2011-11-23

Abstract: Efficient systems to triage increasing numbers of new referrals to breast clinics are needed, to optimise the management of patients with cancer and benign disease. A tool was developed to triage the urgency of referrals and allocate the most appropriate clinician consultation (surgeon or breast physician (BP)).259 consecutive new referrals were triaged using the tool. 100% new cancers and 256 (98.8%) referrals overall were triaged to both appropriate category of urgency and the appropriate clinician.This triage tool provides a simple method for assessing new referrals to a breast clinic and can be easily delivered by trained administrative staff by telephone.

Erysipelas after breast cancer treatment

Kikkeri Narayanashetty Naveen, Varadraj V. Pai, Tukaram Sori, Srinivas Kalabhavi — 2011-09-19

Erysipelas is a distinct type of superficial cutaneous cellulitis with marked dermal lymphatic vessel involvement caused by group A beta hemolytic streptococcus (very uncommonly group C or C streptococcus) and rarely caused by S. aureus. Lymphedema, venous stasis, web intertrigo, and obesity are risk factors in the adult patient. Erysipelas of the upper extremity following breast cancer treatment was vaguely described as a complication in a German-language journal and as a case report in a Dutch-language journal. In a French-language Tunisian medical journal in 2002, erysipelas was described in 20 out of 700 breast cancer patients seen over 6 years with a 20% recurrence rate, and 40% had local trauma as a predisposing injury; however, only 40% had redness, 35% had fever, and 20% had edema. In English language journal 7 cases have been reported out of 310 patients seen over a period of 5 years.

No correlation between plasma D-dimer levels and lymph node involvement in operable breast cancer

2011-12-30

Still unexplored is the correlation between plasma D- dimer levels and axillary node involvement, as detected following SNB investigation, in operable breast cancer. This prospective study attempts to verify the correlation between D - dimer level and lymph node involvement, including patients with positive Sentinel Node.

Isosulfan blue-induced anaphylactic reaction during sentinel lymph node biopsy in breast cancer

2011-12-21

In patients with breast cancer, the most important prognostic factor is whether there exists a metastatic involvement in axillary lymph nodes. Histopathological examination of the sentinel lymph node (SLN) provides information about presence of metastasis in the remaining lymph nodes without application of axillary lymph node dissection. Radiolymphoscintigraphy and/or blue dye is/are used for detection of SLN in breast cancer. Isosulfan blue is the first dye approved by the United States Food and Drug Administration (FDA) in terms of sentinel lymph node biopsy (SLNB), and it is also one of the most commonly used blue dyes. Allergic and anaphylactic reactions to the Isosulfan blue used for SLNB in breast cancer may develop. In our article, we present a case of anaphylactic reaction induced by Isosulfan blue.

Erratum to ‘Sheri A, Dowsett M, Predicting response to cytotoxic drugs – The endocrine part of the story. The Breast, 2011: 20; S28 – S30.’

Amna Sheri, Mitch Dowsett — 2012-01-27

The publisher regrets that there were two errors in the article referenced above, which was published as part of the Proceedings of the 12th St Gallen Primary Therapy of Early Breast Cancer Conference.

Erratum to ‘Goodwin PJ, Stambolic V. Obesity and insulin resistance in breast cancer – chemotherapy strategies with a focus on metformin. The Breast, 2011: 20; S31–S35.’

2012-01-27

The publisher regrets that that there were two errors in the article referenced above, which was published as part of the Proceedings of the 12th St Gallen Primary Therapy of Early Breast Cancer Conference.