Postmenopausal Breast Cancer, Aromatase Inhibitors, and Bone Health: What the Surgeon Should Know.

Breast cancer, as the most common malignancy in women, remains a major public health issue despite countless advances across decades. Endocrine therapy is the cornerstone of treatment of the hormone-sensitive subtype of breast cancer. The use of aromatase inhibitors (AIs) in the postmenopausal women has extended the survival beyond that of Tamoxifen, but harbors a subset of side effects, most notably accelerated bone loss. This, however, does not occur in all women undergoing treatment. It is vital to identify susceptible patients early, to limit such events, employ early treatment thereof, or alter drug therapy. International trials on AIs, predominantly performed in North American and European females, provide little information on what to expect in women in developing countries. Here, surgeons often prescribe and manage endocrine therapy. The prescribing surgeon should be aware of the adverse effect of the endocrine therapy and be able to attend to side effects. This review highlights clinical and biochemical factors associated with decrease in bone mineral density in an, as yet, unidentified subgroup of postmenopausal women. In the era of personalized medical care, appropriate management of bone health by surgeons based on these factors becomes increasingly important.

Impact of a multidisciplinary approach to ultrasound- guided thyroid fine-needle aspiration biopsy at Tygerberg Hospital, Cape Town, South Africa: A retrospective audit.

BACKGROUND: Thyroid nodules are common and mostly benign. Inadequate sampling generally occurs in 13 - 17% of thyroid fine-needle aspiration biopsies (FNABs), but the proportion was found to be as high as 45% on evaluating 100 ultrasound (US)-guided FNABs in a previous unpublished audit at Tygerberg Hospital, Cape Town, South Africa (SA). OBJECTIVES: Primary aim: To determine the diagnostic yield of US-guided thyroid biopsy after implementing changes to existing practices, involving the creation of a specialised clinic and applying protocols for referral and FNAB. Secondary aim: To compare the results with other centres in SA. METHODS: A retrospective audit of 178 thyroid biopsies was conducted. All US-guided thyroid biopsies performed in the specialised clinic between January 2017 and July 2018 were included. Data were analysed using descriptive statistics. RESULTS: The 178 nodules were biopsied in 159 patients. The mean age was 53.7 years, with a gender ratio of 9.6:1 (female/male). A reduction in non-diagnostic biopsies was noted compared with the historical cohort (45% v. 32.6%). Sixty-one nodules (34.3%) had previously been biopsied with inadequate cytology results. When repeat biopsies were excluded, only 16.2% (n=19) were classified as insufficient. CONCLUSIONS: These findings illustrate the importance of the multidisciplinary approach and standardisation of the US-guided biopsy procedure and the value of consistency and quality control in a health system. While nodular thyroid disease is common and FNAB is relatively simple, early referral to a central specialised unit to minimise the incidence of inadequate FNAB should be considered.

A comparison of invasive lobular carcinoma with other invasive breast cancers at Tygerberg Academic Hospital.

BACKGROUND: The second most common histological subtype of invasive breast carcinoma is invasive lobular carcinoma (ILC) occuring with a frequency 10-15% in Western countries and approximately 5%, in Africa, the Middle East and Asia (AMA). Combined hormone replacement therapy (CHRT) is a risk factor for the development of ILC which is infrequently diagnosed at our centre.This study aimed to investigate the incidence and clinicopathological characteristics of ILC as compared to invasive breast carcinoma of no special type (IBC-NST). METHODS: Clinical and pathological data on breast carcinoma patients attending the breast and endocrine unit at Tygerberg Academic Hospital since 2017 have been recorded on a Stellenbosch University REDCap® database. RESULTS: IBC-NST was the most frequent subtype diagnosed (83.9%) and ILC the second most common subtype (5.2%). Most ILCs were of luminal B intrinsic subtype, and the median size was slightly smaller than IBC-NST. There were significantly more grade 2 ILCs than IBC-NSTs (81.5% vs 50.9%). There was no statistical difference between stage and histological subtype. CONCLUSION: ILC has clinicopathological differences when compared to IBC-NST, although these were less pronounced in this study. The prevalence of ILC was similar to numbers reported in AMA. We hypothesise that there may be a discrepancy in the prevalence of ILC between public and private healthcare systems in South Africa, and that it may be due to differing trends in prescribing CHRT.

Pharmacogenetics of Aromatase Inhibitors in Endocrine Responsive Breast Cancer: Lessons Learnt from Tamoxifen and CYP2D6 Genotyping.

BACKGROUND: Genetics play a significant role in drug metabolism of endocrine therapy of breast cancer. These aspects have been studied extensively in patients on tamoxifen, but the pharmacogenetics of aromatase inhibitors are less established. In contrast to the protective effect of tamoxifen, aromatase inhibitors are linked with an increased risk for bone loss and fractures. OBJECTIVE: This review outlines key issues in the implementation of pharmacogenetics of cytochrome P450 and tamoxifen as a model for optimal use of aromatase inhibitors in postmenopausal women with estrogen receptor positive breast cancer. METHODS: Lessons learnt from the association between tamoxifen and CYP2D6 genotyping were applied to identify polymorphisms with the potential to change clinical decision-making in patients on aromatase inhibitors. The ability of next generation sequencing to supersede single-gene analysis was furthermore evaluated in a subset of breast cancer patients on aromatase inhibitors selected from a central genomics database. RESULTS: Methodological flaws in major randomised controlled trials and continued referral to incorrect results in expert consensus statements are important factors delaying the implementation of CYP2D6 pharmacogenetics in tamoxifen treatment. This highlighted the importance of a clinical pipeline including comprehensive genotyping, to define the target population most likely to benefit from aromatase inhibitor pharmacogenetics. CONCLUSION: The clinical utility of CYP2D6 genotyping is well-established in patients at increased risk of tamoxifen resistance due to cumulative risk. The pharmacogenetics of CYP19A1 requires further clarification in terms of bone risk assessment for appropriate use in the treatment algorithm of high-risk patients at the onset of aromatase inhibitors.

Mammographic screening for breast cancer in a resource-restricted environment.

BACKGROUND: Mammographic screening is carried out at public sector hospitals as part of clinical practice. OBJECTIVE: We report the experience of such screening at Tygerberg Academic Hospital (TBAH), a tertiary referral hospital in the Western Cape Province, South Africa. METHODS: All mammograms performed between 2003 and 2012 at TBAH were analysed regarding patient demographics, clinical data, indication and outcome according to the American College of Radiology Breast Imaging Reporting and Data System (BIRADS). Screening mammography was offered to patients > 40 years of age and mammograms were read by experienced breast surgeons. Patients with BIRADS 3 and 4 lesions were recalled for short-term follow-up, further imaging or tissue acquisition. Patients with BIRADS 5 lesions were recalled for tissue acquisition. Further imaging, method of tissue acquisition, histology results and use of neo-adjuvant therapy were also recorded. RESULTS: Of 16 105 mammograms, 3 774 (23.4%) were carried out for screening purposes. The median age of patients undergoing screening was 54 years. Of 407 women with mammograms that were reported as BIRADS 3 - 5 (10.8% of screening mammograms), 187 (46% of recalled women) went on to have further imaging only. Tissue was acquired in 175 patients (43% of recalled women), comprising a biopsy rate of 4.6% of the total series. The malignancy rate in cases in which tissue acquisition was done was 25%. Forty-three breast cancers were diagnosed (11.4/1 000 examinations). Of the cancers, nine (31%) were ductal carcinomas in situ. Of 20 invasive cancers, nine (45%) were < 10 mm in size. Of the invasive cancers, 40% were node-positive. CONCLUSIONS: The cancer diagnosis rate indicates a high breast cancer load in an urbanised population.

Results of a pilot programme of mammographic breast cancer screening in the Western Cape.

BACKGROUND: Mammographic screening programmes are now established in developing countries. We present an analysis of the first screening programme in sub-Saharan Africa. METHODS: Women aged > or = 40 years were identified at three primary healthcare centres in the Western Cape Province, South Africa, and after giving informed consent underwent mammography at a mobile unit. After a single reading, patients with American College of Radiology Breast Imaging Reporting and Data System (BIRADS) 3 - 5 lesions were referred to a tertiary centre for further management. RESULTS: Between 1 February 2011 and 31 August 2012, 2 712 screening mammograms were performed. A total of 261 screening mammograms were reported as BIRADS 3 - 5 (recall rate 9.6%). Upon review of the 250 available screening mammograms, 58 (23%) were rated benign or no abnormalities (BIRADS 1 and 2) and no further action was taken. In 32 women, tissue was acquired (biopsy rate for the series 1.2%); 10 cancers were diagnosed (biopsy malignancy rate 31%). For the entire series of 2 712 screening mammograms, the cancer diagnosis rate was 3.7/1 000 examinations. Of 10 cancers diagnosed at screening, 5 were TNM clinical stage 0, 2 stage I and 3 stage II. CONCLUSIONS: The low cancer detection rate achieved, and the technical and multiple administrative problems experienced do not justify installation of a screening programme using the model utilised in this series.

7-year follow up of intra-operative radiotherapy for early breast cancer in a developing country.

Scarce radiation resources and an often poor, rural population make single fraction, definitive intra-operative radiation (IORT) ideal for developing countries. From 2002 to 2005 IORT in breast conservation was administered utilizing existing infrastructure in an extremely resource-restricted environment. After tumor excision an applicator was introduced into the tumor bed. An existing Ir (192) after loader delivered a single fraction (21 Gy). Of thirty nine patients treated with 84 months follow-up, one patient suffered local, four regional and three systemic relapse. One patient died of disease, 2 of unrelated causes for a local control rate of 95% and a disease-specific survival of 95%. Cosmetic outcome was perceived excellent. IORT using existing after loaders and a low cost applicator greatly reduced health care resources. This extends breast conservation to indigent patients who cannot adhere to lengthy EBRT protocols.

Performance data of screening mammography at a dedicated breast health centre.

BACKGROUND: Mammographic screening has become part of routine health care. We present a first analysis of screening mammography in a dedicated breast health centre in Africa. OBJECTIVE: To establish a performance benchmark and provide data for health care policy and funding decisions on screening mammography. METHOD: All mammography performed between January 2003 and August 2008 was entered into a prospective database. Mammography was performed exclusively by certified mammographers and double-read by experienced readers. RESULTS: Outcomes were classified in a simplified classification system based on the Breast Imaging Reporting and Data System (BIRADS). In 40 - 49-year-old women, 3 192 mammograms led to a recall rate of 4.7%, a biopsy rate of 1.9% and a cancer diagnosis rate of 3.8 per 1 000 examinations; for women of 50 years and older, the corresponding figures were 4 446, 5.4%, 2.6% and 9.7 per 1 000. Of the cancers detected, 31% were in situ and, of the invasive cancers, 81% were node-negative. These figures were established by a dedicated surgeon-led team and fall within the range expected in organised screening programmes in resource-rich environments, providing a first benchmark for screening mammography in Africa.