Fast Facts: Early Breast Cancer

By Jayant S Vaidya and Vivek Patkar

Written for all members of the multidisciplinary breast cancer care team, and for everyone who wishes to know about breast cancer, this concise resource will aid understanding of the risk of developing breast cancer, the essentials of diagnosis and preoperative assessment, and the current approach to treatment and follow-up, with a focus on how each mode of treatment can be optimized to match the individual patient’s needs based on high-quality evidence. Table of Contents: • Etiopathophysiology and risk • Diagnosis • Staging and clinical status • Locoregional treatment • Adjuvant therapy • Survivorship

• Language: English
• Publisher: S. Karger
• Release date: Mar 14, 2023
• ISBN: 9783318070026

Book preview

Introduction

Over the last few decades, we have seen great improvements in our understanding and treatment of breast cancer. Breast cancer has dropped to seventh place on the list of leading causes of death in women worldwide. Such improved survival (from 60% to 90%) has meant that, in the last two decades, there has been increased focus on improving quality of life and minimizing overtreatment. A balanced view of the risks, harms and benefits of any intervention, from screening and diagnosis to the treatment of cancer, is gaining importance.

In this new edition, we outline the importance of triple assessment (clinical examination, imaging and pathology) for a confident diagnosis, including methods of eliciting subtle signs of early cancer such as dimpling (Figure 0.1). We also review key practice-changing evidence in surgery, radiotherapy and systemic therapy.

Advances in technology have made it possible to speed up treatment delivery and minimize side effects without compromising effectiveness. Some of these advances, such as intraoperative radiotherapy, have offered pragmatic solutions to new challenges posed by the recent coronavirus pandemic.

Figure 0.1 Dimpling of skin, seen just above the left nipple here, is a subtle sign of early breast cancer that can be easily missed if one does not look for it. (a) Asking the patient to raise their arms or bend forwards, and (b) examining the breast under good lighting can help to ensure these signs are not missed (see Clinical examination, pages 30–32 for more details).

Figure 0.2 Targeted intraoperative radiotherapy (TARGIT-IORT) is delivered immediately after wide local excision (lumpectomy) surgery for breast cancer (see page 55 for more details).

Following the approach of better targeted surgery, radiotherapy has moved from whole-breast irradiation to targeted radiotherapy (Figure 0.2). Biological/antibody therapy and modulation of the tumor microenvironment is now included as part of systemic therapy in addition to chemotherapy and endocrine therapy. Meanwhile, immunotherapy and targeted treatments such as poly-adenosine diphosphate (ADP) ribose polymerase (PARP) inhibitors have shown promise in triple-negative breast cancer.

The recent surge in artificial intelligence and deep learning capabilities, though in its early days, shows promise of improving the accuracy and speed of diagnosis, aiding clinical decision-making and leading to better outcomes.

Written for all members of the multidisciplinary breast cancer care team, and for everyone who wishes to know about breast cancer, this concise resource will aid understanding of the risk of developing breast cancer, the essentials of diagnosis and preoperative assessment, and the current approach to treatment and follow-up, with a focus on how each mode of treatment can be optimized to match the individual patient’s needs based on high-quality evidence.

1Etiopathophysiology and risk

Definitions

‘Early’ breast cancer refers to cancer that has not spread beyond the breast or the axillary lymph nodes. This includes ductal carcinoma in situ (stage 0) and stage I, IIA, IIB and IIIA invasive breast cancers (see Staging, Chapter 3). The term ‘invasive’ is unique to breast cancer: in no other cancer is such tautology used. It simply means that cancer cells have crossed the basement membrane of the duct and can potentially spread. It is only used because of the popularity of the terms ‘ductal’ or ‘lobular’ carcinoma in situ (DCIS and LCIS) in which cancer cells have not crossed the basement membrane; such lesions, if pure, are theoretically not a risk to life. DCIS and LCIS are usually identified by mammographic screening or as a chance finding after biopsy of a benign lesion. ‘Ductal intraepithelial neoplasia’ would be the preferred name and would remove the unnecessary taboo of cancer when these lesions are diagnosed.

There are no histopathological or molecular markers to accurately predict the progression from DCIS to invasive disease with certainty. Those that are palpable, show comedo necrosis and have higher expression of p16, cyclooxygenase-2 (COX-2) and Ki67, have increased risk. The risk of invasive cancer is believed to increase nine- to elevenfold in a woman in whom DCIS is treated only by removal of the affected area.¹

Incidence and mortality

Worldwide, breast cancer is the most common form of cancer among women, with an estimated 2.26 million new cases diagnosed in 2020.² Although mortality has declined in most areas since 1990,²,³ it is estimated that around 685 000 women worldwide died from breast cancer in 2020, with mortality varying between countries.² However, breast cancer is not the leading cause of death in women; in England, dementia and Alzheimer disease, heart disease, stroke, pneumonia and flu, and lung cancer are higher up the list.⁴ These changing trends in mortality, together with the fact that breast cancer treatments have been linked to a decline in cognitive function,⁵,⁶ have many implications for women when they are making decisions about stopping hormone replacement therapy (HRT) or taking chemotherapy, radiotherapy or endocrine therapy for modest cancer survival benefits.

Structure of the breast and surrounding tissues

The breast is composed of glandular and adipose tissue in varying proportions. The glandular tissue consists of 15–20 lobes containing numerous lobules that are linked by ductules (Figure 1.1). The ductules combine to form the lactiferous ducts, which open into the lactiferous sinuses and empty through the nipple. The breast is enclosed in two layers of fibrous tissue connected by Cooper’s ligaments, which give it its characteristic shape. Invasion of Cooper’s ligaments by cancer shortens the ligaments, leading to the classic early sign of dimpling of the skin when the patient stands with their hands on their hips, contracting the pectoralis. Dimpling is also enhanced when the patient has their arms raised (see Figure 0.1, page 7) or when they bend forwards.

Pathophysiology

Most breast cancers are epithelial tumors, arising from either the milk-producing glands (lobular carcinomas) or, more commonly, the draining ducts (ductal carcinomas); only a small number are non-epithelial, involving the stroma or soft tissues.

Figure 1.1 Structure of the normal breast. The lymphatics of the breast tissue converge in the subareolar plexus of Sappy and then drain into the axilla (armpit); this knowledge is used for localizing the sentinel node by injecting subdermally or intradermally at the edge of the areola.

Ductal carcinomas account for over 90% of breast cancers. Lobular carcinomas account for approximately 8% of breast cancers. Such tumors may occur at several sites, either in one or both breasts. They can be hard to diagnose; their diffuse nature makes them challenging to delineate by palpation and their relative radiolucency makes them difficult to see on mammograms.

Phyllodes tumors are relatively rare stromal tumors that only rarely exhibit the malignant features of a true sarcoma. Clinically and on imaging they resemble fibroadenomas, although they are often more extensive, and occur at a later age.

Receptor status. Estrogen and progesterone are important regulators of normal breast growth and development and play important roles in the pathogenesis of breast cancer. The hormone receptors in some breast cancers promote DNA replication and cell division when estrogen or progesterone bind to them (for example,