Invasive Lobular Breast Cancer as a Distinct Disease: Implications for Therapeutic Strategy

Invasive lobular carcinoma comprises 10–15% of all breast cancers and is increasingly recognised as a distinct and understudied disease compared with the predominant histological subtype, invasive ductal carcinoma. Hallmarks of invasive lobular carcinoma include E-cadherin loss, leading to discohesive morphology with cells proliferating in single-file strands and oestrogen receptor positivity, with favourable response to endocrine therapy. This review summarises the distinct histological and molecular features of invasive lobular carcinoma with focus on diagnostic challenges and the impact on surgical management and medical therapy. Emphasis is placed on recent advances in our understanding of the unique molecular biology of lobular breast cancer and how this is optimising our therapy approach in the clinic

Does Breast Cancer Surgery Impact Functional Status and Independence in Older Patients? A Narrative Review

Surgery is the recommended treatment modality for primary breast cancer. Breast cancer surgery is non-visceral; therefore, it is often assumed that the subsequent impact on functional status in older women is less significant compared to other cancer types such as colorectal cancer. Evidence for this however, is lacking. The definition of functional status varies amongst healthcare professionals and patients, making comparisons between studies difficult. From the literature, the two most common themes in relation to functional status following breast cancer surgery are activities of daily living and quality of life. Both of these elements of functional status are adversely impacted in patients following breast cancer surgery. A more significant decline is seen in patients with pre-existing comorbidities and with greater intensity of surgery, which includes more invasive breast and/or axillary surgery as well as additional reconstructive procedures. Identifying and optimising pre-existing factors which may predict post-operative decline in functional status, such as cognitive impairment and deteriorating functional decline over the preceding year, may help in reducing deterioration in functional status after breast cancer surgery. Methods which may be employed to detect and optimise these factors include geriatric assessment and exercise intervention

Biology of oestrogen-receptor positive primary of core needle biopsy samples and correlation with clinical outcome

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. The majority of biological profiling studies use surgical excision (SE) samples, excluding patients receiving nonsurgical and neoadjuvant therapy. We propose using core needle biopsy (CNB) for biological profiling in older women. Over 37 years (1973–2010), 1 758 older (≥70 years) women with operable primary breast cancer attended a dedicated clinic. Of these, 693 had sufficient quality CNB to construct tissue microarray (TMA). The pattern of biomarkers was analysed in oestrogen receptor (ER)-positive cases, using immunohistochemistry and partitional clustering analysis. The biomarkers measured were: progesterone receptor (PgR), Ki67, Epidermal Growth Factor Receptor (EGFR), Human Epidermal Growth Factor Receptor (HER)-2, HER3, HER4, p53, cytokeratins CK5/6 and CK7/8, Mucin (MUC)1, liver kinase B1 (LKB1), Breast Cancer Associated gene (BRCA) 1, B-Cell Lymphoma (BCL)-2, phosphate and tensin homolog (PTEN), vascular endothelial growth factor (VEGF), and Amplified in breast cancer 1 (AIB1). CNB TMA construction was possible in 536 ER-positive cases. Multivariate analysis showed progesterone receptor (PgR) (p = 0.015), Ki67 (p = 0.001), and mucin (MUC)1 (p = 0.033) as independent predictors for breast-cancer-specific survival (BCSS). Cluster analysis revealed three biological clusters, which were consistent with luminal A, luminal B, and low-ER luminal. The low-ER luminal cluster had lower BCSS compared to luminal A and B. The presence of the low-ER luminal cluster unique to older women, identified in a previous study in SE TMAs in the same cohort, is confirmed. This present study is novel in its use of core needle biopsy tissue microarrays to profile the biology of breast cancer in older women

The impact of tumour biology on the management of primary breast cancer in older women—based on a research programme in Nottingham

The incidence of breast cancer increases with age. Average life expectancies are increasing; the older population is expanding globally. This presents a huge challenge on an international scale in the coming years as more older people are living with breast cancer. Despite this, most research in this field remains focused in younger patients. In this article, we outline the current issues facing understanding of the biology of primary breast cancer in older women with regards to treatment decision making. The main treatment dilemmas concern (I) primary treatment [surgery versus non-operative therapies in estrogen receptor (ER) positive and negative tumours] and (II) adjuvant treatment (such as endocrine therapy or chemotherapy). We then discuss work in this field from the Nottingham Breast Cancer Research Centre, which includes biological assessment of a large (N=1,758) cohort of older (aged ≥70 years) women with primary breast cancer with long-term follow-up data. At a biological level, we understand breast cancer belongs to four main subtypes [luminal A, luminal B, human epidermal growth factor receptor 2 (HER2) over-expression, or triple negative breast cancer (TNBC)], with treatment plans based upon these. The Nottingham group have found a biological cluster unique to older women with primary breast cancer (low ER luminal type), which is not seen in their younger (< 70 years) counterparts, as well as differences between age and clinical outcome in patients with ER-positive, HER2-positive and TNBC. This adds further evidence that the biology of breast cancer in older women is different to that of younger women and therefore, should be treated as such. Finally; we outline future considerations to achieve personalised breast cancer treatment in this cohort which includes optimisation of biological assessment with integrated geriatric assessment

Molecular Biomarker Expression in Window of Opportunity Studies for Oestrogen Receptor Positive Breast Cancer: A Systematic Review of the Literature

Window of opportunity (WoO) trials create the opportunity to demonstrate pharmacodynamic parameters of a drug in vivo and have increasing use in breast cancer research. Most breast cancer tumours are oestrogen receptor-positive (ER+), leading to the development of multiple treatment options tailored towards this particular tumour subtype. The aim of this literature review is to review WoO trials pertaining to the pharmacodynamic activity of drugs available for use in ER+ breast cancer in order to help guide treatment for patients receiving neoadjuvant and primary endocrine therapy. Five databases (EMBASE, Cochrane, MEDLINE, PubMed, Web of Science) were searched for eligible studies. Studies performed in treatment-naïve patients with histologically confirmed ER+ breast cancer were included if they acquired pre- and post-treatment biopsies, compared measurement of a proteomic biomarker between these two biopsies and delivered treatment for a maximum mean duration of 31 days. Fifteen studies were eligible for inclusion and covered six different drug classes: three endocrine therapies (ETs) including aromatase inhibitors (AIs), selective oestrogen receptor modulators (SERMs), selective oestrogen receptor degraders (SERDs) and three non-ETs including mTOR inhibitors, AKT inhibitors and synthetic oestrogens. Ki67 was the most frequently measured marker, appearing in all studies. Progesterone receptor (PR) and ER were the next most frequently measured markers, appearing five and four studies, respectively. All three of these markers were significantly downregulated in both AIs and SERDs; Ki67 alone was downregulated in SERMs. Less commonly assessed markers including pS6, pGSH3B, FSH and IGF1 were downregulated while CD34, pAKT and SHBG were significantly upregulated. There were no significant changes in the other biomarkers measured such as phosphate and tensin homolog (PTEN), Bax and Bcl-2.WoO studies have been widely utilised within the ER+ breast cancer subtype, demonstrating their worth in pharmacodynamic research. However, research remains focused upon routinely measured biomarkers such ER PR and Ki67, with an array of less common markers sporadically used

Immediate breast reconstruction uptake in older women with primary breast cancer: systematic review.

BackgroundPostmastectomy immediate breast reconstruction (PMIBR) may improve the quality of life of patients with breast cancer, of whom older women (aged 65 years or more) are a growing proportion. This study aimed to assess PMIBR in older women with regard to underlying impediments (if any).MethodsMEDLINE, Embase, and PubMed were searched by two independent researchers up to June 2022. Eligible studies compared PMIBR rates between younger and older women with invasive primary breast cancer.ResultsA total of 10 studies (2012–2020) including 466 134 women were appraised, of whom two-thirds (313 298) were younger and one-third (152 836) older. Only 10.0 per cent of older women underwent PMIBR in contrast to 45.0 per cent of younger women. Two studies explored factors affecting uptake of PMIBR in older women; surgeon-associated (usual practice), patient-associated (socioeconomic status, ethnicity, and co-morbidities), and system-associated (insurance status and hospital location) factors were identified.ConclusionUptake of PMIBR in older women is low with definable (and some correctable) barriers