Nicola Roche

Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled trial

BACKGROUND Aromatase inhibitors effectively prevent breast cancer recurrence and development of new contralateral tumours in postmenopausal women. We assessed the efficacy and safety of the aromatase inhibitor anastrozole for prevention of breast cancer in postmenopausal women who are at high risk of the disease. METHODS Between Feb 2, 2003, and Jan 31, 2012, we recruited postmenopausal women aged 40-70 years from 18 countries into an international, double-blind, randomised placebo-controlled trial. To be eligible, women had to be at increased risk of breast cancer (judged on the basis of specific criteria). Eligible women were randomly assigned (1:1) by central computer allocation to receive 1 mg oral anastrozole or matching placebo every day for 5 years. Randomisation was stratified by country and was done with blocks (size six, eight, or ten). All trial personnel, participants, and clinicians were masked to treatment allocation; only the trial statistician was unmasked. The primary endpoint was histologically confirmed breast cancer (invasive cancers or non-invasive ductal carcinoma in situ). Analyses were done by intention to treat. This trial is registered, number ISRCTN31488319. FINDINGS 1920 women were randomly assigned to receive anastrozole and 1944 to placebo. After a median follow-up of 5·0 years (IQR 3·0-7·1), 40 women in the anastrozole group (2%) and 85 in the placebo group (4%) had developed breast cancer (hazard ratio 0·47, 95% CI 0·32-0·68, p<0·0001). The predicted cumulative incidence of all breast cancers after 7 years was 5·6% in the placebo group and 2·8% in the anastrozole group. 18 deaths were reported in the anastrozole group and 17 in the placebo group, and no specific causes were more common in one group than the other (p=0·836). INTERPRETATION Anastrozole effectively reduces incidence of breast cancer in high-risk postmenopausal women. This finding, along with the fact that most of the side-effects associated with oestrogen deprivation were not attributable to treatment, provides support for the use of anastrozole in postmenopausal women at high risk of breast cancer. FUNDING Cancer Research UK, the National Health and Medical Research Council Australia, Sanofi-Aventis, and AstraZeneca.

How safe is oncoplastic breast conservation?: Comparative analysis with standard breast conserving surgery

AIM Oncoplastic techniques are increasingly used to facilitate breast conservation and maintain breast aesthetics but evidence with regards to the oncological safety of oncoplastic breast conservation surgery (oBCS) remains limited. The aim of this study was to compare re-excision and local recurrence rates for oBCS with standard breast conserving surgery (sBCS). METHODS From June 2003 to Feb 2010 data was obtained from contemporaneously recorded electronic patient records on patients who had oBCS and sBCS within a single breast cancer centre. Re-excision rates and local recurrence rates were compared. RESULTS A total of 440 sBCS and 150 oBCS (in 146 women) were included in this study. Median tumour size and specimen weight was 21 mm and 67 g for oBCS and 18 mm and 40 g in the sBCS group (p < 0.001). Re-excision was 2.7% (4/150) and 13.4% (59/440) for oBCS and sBCS respectively (p < 0.001). At a median follow-up of 28 months, local relapse was 2.7% (4) and 2.2% (10) and distant relapse 1.3% (2) and 7.5% (33) for oBCS and sBCS respectively. CONCLUSIONS Oncoplastic breast conserving techniques decrease re-excision rates. Early follow up data suggests oncological outcomes of oncoplastic breast conservation surgery are similar to standard breast conservation.

Correlation of Age and HRT Use with Breast Density as Assessed by Quantra

Breast density is a significant predictor in the risk of developing breast cancer. Several methods are available for assessing breast density, but most are subject to intra‐observer variability and are unable to assess the breast as a three‐dimensional structure. Using Quantra™ to quantify breast density, we have correlated this with risk factors to determine what impact these variables have on breast density. Women attending for full field digital mammography at the South West London Breast Screening Unit between December 2008 and March 2009 were invited to participate in the study by questionnaire. Consenting women returned the questionnaire allowing further data collection including demographics, menopausal status and hormone replacement therapy (HRT) use. Data were correlated against breast density measurements to determine the degree of association. Mammograms were assessed on a Hologic™ workstation and breast density calculated using Quantra™. Quantra™ is an automated algorithm for volumetric assessment of breast tissue composition from digital mammograms. Six‐hundred and eighty‐three women were invited to participate. Those with implants or mastectomy were excluded. Three‐hundred and twenty questionnaires were fully completed and able to be assessed. The mean age of participants was 59 years (range 49–81). Mean density was 19.7% (range 8.5–48.5%). There was a decrease in density with age (Pearson product‐moment correlation coefficient −0.17). Correlation between density and HRT use showed a significant positive result (correlation coefficient 0.07). Quantra™ has shown to be an accurate, reproducible tool for quantifying breast density, demonstrated by its correlation with lifestyle and demographic data. Given its ease of acquisition this may be the future of breast density quantification in the digital age.

Follow-up after treatment for breast cancer in young women.

The majority (80%) of breast cancers are diagnosed in women over the age of 50; only 5% will be in their 20s and 30s. These women have specific needs that include genetic counselling, psychological support, advice with regard to fertility and pregnancy issues and information on coping with treatment-related morbidity. The primary purpose of follow-up is often regarded as the early detection of recurrence as well as the detection of second primary tumours. Rather than concentrating solely on detecting cancer recurrence, clinicians need to be more susceptive to symptoms related to treatment morbidity and to the information needs of their patients. This paper outlines the specific issues listed above that need to be addressed in follow-up clinics and highlights interventions that may help improve the value of follow-up appointments and quality of life for young women with breast cancer.

Axillary nodal yields: A comparison between primary clearance and completion clearance after sentinel lymph node biopsy in the management of breast cancer

AIMS Axillary nodal status is the most important prognostic indicator which in turn influences adjuvant therapy and long term outcomes. The aim of this study was to compare total nodal yields from primary axillary lymph node dissection (pALND) with completion ALND after a cancer positive SLNB: either concurrently (cALND) following intra-operative assessment (IOA) of the SLNs or as a delayed procedure (dALND) when the SLN was found to be cancer positive on post-operative histological examination. METHODS All axillary procedures performed between May 2006 and September 2009 were identified from a prospective database and categorised into four groups: SLNB with no further axillary surgery, pALND, cALND and dALND. Total nodal yield was the sum of SLN/s and ALND yields. RESULTS Of 1025 axillary procedures, ALND accounted for 332 (32.4%) of which 207 (62.3%) underwent pALND, 43 (12.9%) cALND, and 82 (24.6%) dALND. Median nodal yields were 15.0, 16.0 and 14.5 respectively (p = 0.3). CONCLUSION Total nodal yields for primary, concurrent and delayed ALND were comparable suggesting completion dALND performed as a second operation does not compromise axillary staging.

Sclerosing lymphocytic lobulitis of the breast

Abstract Sclerosing lymphocytic lobulitis of the breast is an uncommon condition which clinicians need to be aware of. The disorder has characteristic pathological features; however, findings on triple assessment may be equivocal. In this paper we report ten cases of sclerosing lymphocytic lobulitis and outline the clinical, cytological and radiological features of this condition. Patients, often diabetic, typically present with discrete firm breast lumps. Fine needle aspiration cytology is either acellular or benign and mammography is normal or indeterminate whereas ultrasonography is usually suspicious of malignancy. If the condition is recognized prior to surgery, excision biopsy in patients who are often diabetic may be avoided.

Should patients with ductal carcinoma in situ be treated with adjuvant whole breast radiotherapy after breast conservation surgery

### What you need to know Ductal carcinoma in situ (DCIS) affects around 8000 women a year in the UK.1 Since the introduction of mammographic screening, the incidence of DCIS has increased and it now represents around 20% of all new screen detected breast cancers.2 DCIS is categorised into low, intermediate, and high grade based on histological features. Most cases of DCIS are treated with breast conserving surgery (BCS), often followed by whole breast radiotherapy (WBRT). An individual patient level meta-analysis (four randomised controlled trials, 3729 women) found that WBRT approximately halved the rate of ipsilateral DCIS or invasive recurrence at 10 years compared with no radiotherapy following BCS.3 However, WBRT can cause side effects such as impaired cosmesis, skin changes, and late cardiac toxicity4 Patients might also find WBRT inconvenient and expensive. National Institute of Health and Care Excellence (NICE) guidelines recommend offering WBRT to all patients with DCIS treated by BCS.5 The European Society of Medical Oncology guidelines suggest that WBRT might be omitted in some low risk patients.6 However, observational studies done in the UK, US, and Europe note wide variations in the use of adjuvant radiotherapy in these patients.7 This variation possibly reflects uncertainty as to whether the benefits of WBRT are large enough to warrant the blanket use of adjuvant WBRT or whether WBRT can be safely omitted in a subset of lower risk patients. In this article we discuss the evidence surrounding radiotherapy use in …

Detection of Recurrence: Clinical Follow-Up

Breast cancer follow up after treatment of early disease has evolved in recent years to allow for a more patient centered approach. Various models of follow up successfully exist, aiming to provide early detection of treatable local recurrence in the ipsilateral or contra-lateral breast, identify symptoms suggestive of secondary breast cancer and to support patients who may have treatment related sequelae, albeit physical or emotional. A novel model for a patient-led approach is outlined in detail.

Abstract S3-01: Breast cancer prevention using anastrozole in postmenopausal women at high risk

Background: Third generation aromatase inhibitors are the most effective endocrine treatment for hormone receptor positive breast cancer in postmenopausal women. Here, we assess the efficacy of anastrozole in postmenopausal women who do not have breast cancer, but are at high risk of developing the disease. Methods: A multi-centre randomised placebo-controlled trial of 1mg/day oral anastrozole vs. matching placebo for five years was conducted in 3864 postmenopausal women at increased risk of breast cancer. The primary endpoint was the incidence of breast cancer (including ductal carcinoma in-situ (DCIS) and differences were assessed by the proportional hazards model. Detailed information on adverse events was collected. Results: After a median follow up of 5.03 years, 125 breast cancers were recorded. A 53% reduction (95% CI (32-68%), P<0.0001) was seen in the anastrozole arm. Significant reductions were seen for all invasive (50%), oestrogen receptor positive invasive (58%) and in situ tumours (70%). Fractures were non-significantly higher (8.5% vs. 7.7%, P = 0.3) and musculoskeletal events were significantly higher in the anastrozole arm (1226 vs. 1124, RR = 1.10 (1.05-1.16)) but were very common in both arms (63.9% vs. 57.8%). Vasomotor symptoms were also increased with anastrozole (RR = 1.15 (1.08-1.22)). Cancers at other sites were significantly decreased (40 vs. 70, RR = 0.58 (0.39-0.85)). Deaths from breast cancer and other causes were similar in both arms. Conclusions: Anastrozole is an effective agent for reducing breast cancer incidence in postmenopausal women at high risk. Anastrozole was well tolerated and side effects associated with oestrogen deprivation were only slightly higher than for placebo. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr S3-01.

Abstract P1-01-11: Is OSNA mRNA copy number in sentinel lymph node biopsy predictive of further disease in the axilla?

Introduction: Intra-operative assessment of sentinel nodes (SLNs) allows immediate completion axillary dissection (cALND) in breast cancer patients. Molecular assessment such as one-step nucleic acid amplication (OSNA) promises greater sensitivity and provides a more accurate quantitative assessment than traditional methods. Our unit policy is to proceed to cALND in patients with macrometastases but not for micrometastases. However, evidence of upstaging has led us to seek to raise the threshold for proceeding to cALND. The CK19 mRNA copy number is an expression of the metastatic burden in the SLN and may be related to the presence of additional disease in the cALND. Since the original copy number threshold between micro (250–5000 copies/microliter) and macrometastasis (>5000 copies/microliter) was based on few patients and serial pathological sections, we investigated the mRNA copy number in patients with and without additional disease in the cALND. Methods: All patients in our unit undergo pre-operative axillary ultrasound with fine needle aspiration cytology of any suspicious nodes. Those with malignant cytology proceed directly to ALND. Radiologically and cytologically node negative patients undergo sentinel lymph node biopsy (SLNB) and OSNA. Electronic records of consecutive patients with invasive breast cancer undergoing SLNB with OSNA from August 2011 to March 2012 were retrospectively reviewed. Two parameters of mRNA copy number were examined: Copy number of the highest copy number SLN and the summed copy numbers of all positive SLNs. Their relationship to the presence of further disease in the axilla was examined using Student9s t test. Results: Of 201 SLNBs, 45 (22%) had macrometastasis-positive OSNA and therefore underwent cALND (1 patient declined). Twenty patients (45%) had no further positive nodes (a negative cALND) with a total axillary metastatic burden of 1–2 in 11–27 nodes. Twenty four (55%) showed further disease (a positive cALND) with a burden of 2–20 in 9–30 nodes, including the SLNs. There was no significant difference in tumour size or grade between patients with additional positive nodes in the cALND compared with those with no further disease. There was no significant difference in the copy number of the highest copy number positive SLN (p = 0.44) or in the summed copy number of all positive SLNs (p = 0.36) between the cALND positive and negative groups. Conclusion: OSNA CK19 mRNA copy number does not correlate with the cALND metastatic burden. Therefore, raising the copy number threshold may be too simplistic as a method to better select patients with high probability of a positive cALND. A predictive model will be derived based on multivariate analysis of the larger patient population (>400 patients) that will have undergone SLNB with OSNA by the time of SABCS. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-01-11.