Challenges and clinical relevance of modern breast pathology reporting - your questions answered.

BACKGROUND: Breast pathology reporting, especially for breast cancer, has evolved through the years, from terse succinct diagnostic conclusions with scant histological details to the current comprehensive reporting guidelines issued by major pathology colleges and bodies, including the International Collaboration on Cancer Reporting. Pathology elements included in reporting guidelines are evidence based and contribute significantly to individualised and personalised patient management. SUMMARY: This article is based on the lively interactive question and answer session that followed the breast pathology segment in the symposium jointly organised by the British Association of Urological Pathology, British Association of Gynaecological Pathologists, British Society of Gastroenterology and the Association of Breast Pathology, in November 2022, titled 'Personalised histopathology reporting for personalised medicine'. KEY MESSAGES: The breast pathology session emphasized the clinical utility of breast pathology data items, incorporating a case-based approach by highlighting the relevance of pathology information in various clinical scenarios. This review included clinico-pathological discussion points on florid lobular carcinoma in situ (LCIS), atypical apocrine adenosis, post-neoadjuvant chemotherapy reporting, atypical ductal hyperplasia (ADH) presenting at the margin, flat epithelial atypia (FEA) vs columnar cell change (CCC), papilloma on core needle biopsy (CNB), margin status, mucocele-like lesion, total duct excision/microdochectomy specimen, and anterior and nipple margins in skin-sparing mastectomy. Effective communication and regular involvement of pathologists in breast multidisciplinary tumour boards are crucial.

The frequency and clinical significance of centromere enumeration probe 17 alterations in human epidermal growth factor receptor 2 immunohistochemistry-equivocal invasive breast cancer.

BACKGROUND AND AIMS: Chromosome 17 alterations affect the assessment of HER2 gene amplification in breast cancer (BC), but its clinical significance remains unclear. This study aimed to identify the prevalence of centromere enumeration probe 17 (CEP17) alterations, and its correlation with response to neoadjuvant therapy (NAT) in BC patients with human epidermal growth factor receptor 2 (HER2) immunohistochemistry-equivocal score. METHODS AND RESULTS: A large BC cohort (n = 6049) with HER2 immunohistochemistry score 2+ and florescent in-situ hybridisation (FISH) results was included to assess the prevalence of CEP17 alterations. Another cohort (n = 885) with available clinicopathological data was used to evaluate the effect of CEP17 in the setting of NAT. HER2-amplified tumours with monosomy 17 (CEP17 copy number < 1.5 per nucleus), normal 17 (CEP17 1.5-< 3.0) and polysomy 17 (CEP17 ≥ 3.0) were observed in 16, 59 and 25%, respectively, compared with 3, 74 and 23%, respectively, in HER2-non-amplified tumours. There was no significant relationship between CEP17 alterations and pathological complete response (pCR) rate in both HER2-amplified and HER2-non-amplified tumours. The independent predictors of pCR were oestrogen (ER) negativity in HER2-amplified tumours [ER negative versus positive; odds ratio (OR) = 11.80; 95% confidence interval (CI) = 1.37-102.00; P = 0.02], and histological grade 3 in HER2 non-amplified tumours (3 versus 1, 2; OR = 5.54; 95% CI = 1.61-19.00; P = 0.007). CONCLUSION: The impacts of CEP17 alterations are not as strong as those of HER2/CEP17 ratio and HER2 copy number. The hormonal receptors status and tumour histological grade are more useful to identify BC patients with a HER2 immunohistochemistry-equivocal score who would benefit from NAT.

Management of the axilla following neoadjuvant chemotherapy for breast cancer- A change in practice.

OBJECTIVES: Chemotherapy in the neo adjuvant setting has allowed downsizing of breast tumours thus allowing patients to benefit from breast conservation surgery. The effect of neoadjuvant chemotherapy (NAC) has also been observed in the axilla but most units are still treating the axilla with axillary lymph node dissection (ALND). MATERIALS AND METHODS: A prospective database of breast cancer patients receiving NAC between 2007 and 2016 at a single breast unit was reviewed. The management of the axilla and outcomes was studied. RESULTS: 165 patients received NAC, 123 (74.5%) were clinically/radiologically node positive and 42 were negative. Median age was 50 years. 26.7% had triple negative disease and 34.5% were HER2 positive. 56/123 (45.5%) patients with positive nodes at the outset responded completely to NAC. 40 patients with positive nodes pre-NAC had post NAC SLNB with 37 requiring adjuvant radiotherapy only. 83/123 went directly to ALND post NAC and of these 27 were node negative and therefore may be considered to have had an unnecessary ALND. Overall mortality was 20.6% (34), local recurrence in the breast or mastectomy scar was 3.6% (6) but there was no recurrence in the axilla (0/165) with a median follow up of 67 months. CONCLUSION: There is no clear evidence for management of the axilla post NAC. We have used best available evidence to change our practice over the years and our results should encourage others to de-escalate treatment of the axilla in line with the recently published multidisciplinary guidance on axillary surgery following neoadjuvant chemotherapy.

The association of breast surgery ASPIRE: breast pain pathway rapid evaluation project - study protocol.

Background: Breast pain accounts for 20-40% of new referrals to breast units in the UK and these patients have a very low risk of breast cancer. Patients have previously been assessed in resource-intensive, cancer-exclusion, one stop clinics, which are now failing to meet government targets due to excessive demand. UK Breast units are increasingly piloting Breast Pain-only Pathways (BPP) to assess these patients, and there is no consensus for the optimal pathway. The aim of this prospective multicentre study is to assess the safety and patient satisfaction of different BPPs to inform future BPP design and implementation. Methods: All UK breast units will be invited to join the ASPIRE study between January 2023 and December 2023. Units with a BPP are invited to submit their pathway for evaluation; and those without a BPP who see patients with breast pain-only in a one stop clinics setting are also invited to join the study to evaluate the traditional pathway model concurrently. Patient satisfaction assessments will be collected after their initial consultation and patient outcomes, including subsequent cancer diagnosis, will be followed up at 12 months to determine if they have cancer diagnosis after discharge to assess pathway safety.

Factors leading to the late diagnosis and poor outcomes of breast cancer in Matabeleland South and the Bulawayo Metropolitan Provinces in Zimbabwe.

INTRODUCTION: Breast cancer (BC) is the leading cause of female cancer deaths in Africa, and in Zimbabwe, >80% present with advanced disease. A Needs Project (NP) was carried out to determine the key factors responsible for delayed diagnosis and poor BC outcomes and to investigate possible solutions in 6 rural and urban districts of Matabeleland South and Bulawayo Metropolitan Provinces. METHODS: A mixed method approach was used to collect data in 2 phases. Phase 1: an exploration of key factors leading to poor BC outcomes with >50 professional stakeholders and patient representatives. Phase 2: (i) Quantitative arm; validated questionnaires recording breast cancer knowledge, demographic information and perceived barriers to care administered to women and their relatives (Group 1) and health professionals (HPs) (Group 2). (ii) Qualitative arm; 10 focus group discussions with medical specialists and interested lay representatives (Group 3). The Cochran sample size formulae technique was used to determine the quantitative sample size and data was aggregated and analysed using SPSS Version 23™. Purposive sampling for the qualitative study selected participants with an understanding of BC and the NP. Focus group discussions were recorded and a thematic analysis of the transcriptions was conducted using NVivo9™. RESULTS: Quantitative analysis of Group 1 data (n = 1107) confirmed that younger women (<30years) had the least knowledge of breast cancer (p<0.001). Just under half of all those surveyed regarded breast cancer as incurable. In Group 2 (n = 298) the largest group of health workers represented were general nurses and midwives (74.2%) in keeping with the structure of health provision in Zimbabwe. Analysis confirmed a strong association between age and awareness of BC incidence (p = 0.002) with respondents aged 30-39 years being both the largest group represented and the least knowledgeable, independent of speciality. Nearly all respondents (90%) supported decentralisation of appropriate breast surgical services to provincial and district hospitals backed up by specialist training. Thematic analysis of focus group discussions (Group 3) identified the following as important contributors to late BC diagnosis and poor outcomes: (i) presentation is delayed by poorly educated women and their families who fear BC and high treatment costs (ii) referral is delayed by health professionals with no access to training, skills or diagnostic equipment (iii), treatment is delayed by a disorganised, over-centralized patient pathway, and a lack of specialist care and inter-disciplinary communication. CONCLUSION: This study confirms that the reasons for poor BC outcomes in Zimbabwe are complex and multi-factorial. All stakeholders support better user and provider education, diagnostic service reconfiguration, targeted funding, and specialist training.

Ethnicity and breast cancer in the UK: Where are we now?

Outcomes from breast cancer for women in the UK have improved significantly over recent decades. These gains are largely attributable to a combination of earlier diagnosis and access to treatments delivered to patients by the National Health Service irrespective of cost. Ethnic minority groups make up almost fifteen percent of the UK population and there is concern however that these groups may have poorer outcomes from the disease. In this short report we seek to summarise what the current evidence tells us about the patterns of breast cancer incidence and outcomes in ethnic minority women in the UK in order to raise awareness about this topic and provide consideration for what future research is needed to address the gaps that may exist.

Radioguided occult lesion localisation (ROLL) is available in the UK for impalpable breast lesions.

INTRODUCTION: To test the feasibility and reliability of ROLL in a district general hospital (DGH) dealing with screening detected breast lesions. PATIENTS AND METHODS: [(99m) Tc]-labelled colloidal human serum albumin was injected in the core of the breast lesion under ultrasound or stereotactic guidance 2-4 h prior to surgery. At operation, the radioactivity is localised using a gamma-probe. This allows optimal placement of the skin incision and subsequent WLE of the abnormal area. RESULTS: ROLL was utilised on 36 patients (median age, 61 years; range, 43-75 years); of these, 33 B5 lesions had a therapeutic one-step procedure (lumpectomy and axillary dissection) and 3 B4 patients had the lesion excised for diagnostic purposes. Localisation lasted a median of 8 min (range, 5-15 min), ROLL-guided wide tumour excision lasted 20 min (range, 15-30 min), and median postoperative hospital stay was 2 days (range, 1-3 days). Median cancer diameter was 12 mm (range, 6-40 mm). Margins were clear in 29 patients, while 7 patients with DCIS had involved margins. Median minimal clearance was 5 mm (range, < 1-10 mm). Patients had either excellent (24/36) or good (12/36) cosmetic results. CONCLUSIONS: ROLL successfully localised all lesions; this technique can be implemented in any DGH with a Nuclear Medicine Department. The learning curve is short, cost effectiveness is proven, and cosmetic results are highly rewarding. ROLL could rapidly become the standard localisation technique in the UK.