Breast Flashcards
What are the types of pre-invasive breast carcinomas?
Ductal Carcinoma In Situ (DCIS)
DCIS is a neoplasm of the epithelial cells lining the ducts. It is associated with an inherent, but not inevitable, risk of progression to invasive breast carcinoma. It is common and incidence has markedly increased since the introduction of breast screening programmes.
As patients with DCIS have the highest risk of developing invasive breast carcinoma, these are the patients screening programs are designed to triage.
- 85% present on screening mammography (due to microcalcification)
- 10% present with symptoms (lump, nipple discharge, eczematous change of the nipple = Paget’s disease of the nipple)
- 5% incidentally.
- Histology shows ducts filled with atypical epithelial cells.
Graded into low, intermediate or high grade according to degree of nuclear atypia.
- Low-grade DCIS : punched out spaces, calcified debris,
- High-grade DCIS: Large cells, pleomorphic, occluded lumen with a lot of debris in centre
Treatment with surgical excision with clear margins is very successful, usually curative. Recurrence is more likely with extensive disease and high grade DCIS (mastectomy suggested).
Lobular Carcinoma In Situ (LCIS)
LCIS are always incidental finding on biopsy as there are no microcalcifications or stromal reactions. 20-40% are bilateral.
Cells lack adhesion protein E-cadherin which explain the histopathologic appearance of LCIS including a diffuse growth pattern of this non-gland-forming tumour with discohesive tumor cells. Progresses to lobular invasive breast carcinoma (second most common type of invasive breast carcinoma).
What are the histological subtypes of breast cancer?
Several histological types are recognised:
- Ductal (80%) – cells are enlarged, pleomorphic, blue clumpy chromatin, hardly any cytoplasm (nucleomegaly)
- Lobular (15%) – linear arrangement, monomorphic (cell size doesn’t vary much), Indian file pattern
- Tubular (5%) – little tubules, elongated
- Mucinous (5%) – lots of mucins
- Basal-Like Carcinoma - often seen with BRCA mutations, histologically seen as sheets of markedly atypical cells with prominent lymphocytic infiltrate
Describe the prognostic value of receptor status in breast cancer
Receptor status is important as it provides a target for treatment but also carries a prognostic value:
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Low grade types tend to be ER, PR positive and Her2 non-amplified
- Tend to arise from low grade DCIS or in situ lobular neoplasia and show 16q loss
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High grade types tend to be ER, PR negative and Her2 amplified
- Tend to arise from high grade DCIS and show complex karyotypes with many unbalanced chromosomal aberrations
- Basal-like are often ER/PR/Her2 negative (triple negative)
What are the risk factors for breast cancer?
Risk factors for breast cancer include:
- Sex - 100x higher in women than in men
- Age - The incidence of breast cancer doubles every 10 years until menopause, after which the increase slows down.
- Geographical variance/race - Breast cancer rates around the world are similar, until after the age of 50. Generally, incidence is greatest in Caucasians. [Interesting study where they compared incidence in Japanese women in Japan, Hawaii and America; they found that incidence was greatest in American Japanese women, followed by Hawaiian, and lowest in Hawaiian Japanese women].
- High socioeconomic class - may be due to increased diagnosis, or exogenous hormone use.
- Positive family history/genetic predisposition. Although only 5% of breast cancers are due to strong genetic predisposition, genetic predisposition may play an important part in the development of the other 95% of breast cancers. The risk ratio for breast cancer rises with increasing numbers of affected relatives. The risk ratios are 1.8, 2.93, and 3.9 for women with 1, 2, and ≥3 affected first-degree relatives, respectively.
- Early age at menarche and late age of menopause - increased endogenous oestrogen exposure.
- Late age of parity - women who have their first child before the age of 18 have a breast cancer risk that is one third of the risk of patients who first become pregnant after the age of 35 years.
- Exogenous oestrogen/progestogen exposure - oral contraceptive pill or HRT
Other strong risk factors include: high levels of alcohol consumption, radiation exposure, previous benign breast disease, and increased breast density.
What are the clinical features of breast cancer?
Screen-detected cancer is usually asymptomatic, as otherwise it wouldn’t have been screen detected.
Symptomatic cancer usually presents with a painless increasing mass (see Breast Lump Assessment). A lump that is ill-defined and immobile points towards cancer.
There may also be nipple symptoms such as discharge (only 5-10% of patients with bloodstained discharge have malignancy). Spontaneous discharge can be a sign (but also normal is lots of patients), all patients with that should be examined. Nipple retraction (a slit-like nipple) is a sign of benign disease, but nipple inversion is a sign of breast cancer and breast inflammation.
Other skin changes include:
- Skin dimpling due to fibrosis in the connective tissue.
- Paget’s disease of the breast - an eczema-like rash on breast and nipple
- Skin ulceration
- Peau de Orange
Breast pain is only rarely a symptom of cancer, but is a sign of other breast diseases.
What are the investigations for breast cancer?
Triple assessment is the combination of:
- Physical examination
- Imaging (if ≥35 years old then mammography with or without ultrasound, if <35 then ultrasound only).
- Core biopsy, FNAC or both.
Mammography is X-raying the breast tissue. Two views - oblique and cranio-caudal are obtained. Breasts are relatively radiodense, so should not be performed in women under 35 years of age, unless cancer is clinically suspected. Mammography can show lesions of mass, areas of parenchymal distortion, and microcalcifications.
Ultrasonography is quite useful. Breast Cysts show up as transparent objects. Other benign lesions tend to have well-demarcated edges, whereas cancerous lesions have indistinct outlines.
MRI is an accurate method of imaging the breast tissue. It is very sensitive to breast cancers, but not very specific. It is therefore mainly used to assess the extent of invasive lobular cancers, and also the response of neoadjuvant therapies.
After biopsy, cytology is usually used to test for hormone receptors such as oestrogen receptor (ER), and progestogen receptor (PR). HER2 receptor testing is also important. Identifying these guide management and prognosis.
Describe the management of breast cancer
