2: Invasive Breast Carcinoma

Invasive breast carcinoma is the most common malignancy in women after the non-melanomatous skin cancers. There are a number of pathological subtypes of invasive breast carcinoma but this group is thought to arise from the epithelium lining the ducts of the terminal duct lobular unit (see Anatomy of the Breast).

Epidemiology

Invasive carcinoma of the breast is the most common malignancy in women, more than doubling the incidence of malignancies of other individual sites. About 6% of women in Western, developed nations will develop breast cancer by the age of 75. Developing nations have slightly lower rates of invasive breast carcinoma but it remains a common cause of cancer in all populations.
Environmental factors are thought to be particularly important as people from one geographic area tend to assume the risk of their new region after 1 - 2 generations
Breast cancer in men is considered separately.

Summary
Most common cancer of women
More common in Western countries (6% lifetime risk)
Important environmental factors


Aetiology

There are five major aetiologies of breast cancer:

  • Western lifestyle (low exercise, high calorie diet)
  • Hormonal factors (early menarche, late menopause, timing and number of pregnancies, hormone replacement therapy)
  • Ionising radiation
  • Germline mutations of tumour suppressor genes (BRCA1/BRCA2)
  • Benign breast cancers

These have been identified through large population studies. The exact effects of diet are not well known, with fibre typically thought protective and fats a risk factor.

Pathogenesis

The pathogenesis of breast cancer is still under research.
An important factor may be insulin and insulin growth factor 1 (IGF-1) - these hormones increase the biologically available oestrogens and may increase the risk of breast cancer. This could explain the effect of the Western diet on breast cancer rates.

Natural History

Pre-Invasive Lesions

Pre-invasive lesions are discussed in the non-invasive breast carcinoma topic.
ER/PR +ve breast carcinoma is thought to arise on a continuum of gradual steps:

  • Normal ductal epithelium
  • Ductal hyperplasia
  • Atypical ductal hyperplasia
  • Ductal carcinoma in situ
  • Invasive carcinoma

ER/PR -ve carcinoma is less well understood; it can definitely arise from ER/PR -ve DCIS (often high grade) but the precursor lesion for ER/PR -ve DCIS is unknown.

Patterns of Spread

Breast carcinoma is known for local invasion, lymphatic spread and haematogenous spread.

  • Local invasion may occur through the breast parenchyma. Extensive local invasion can lead to chest wall involvement (T4a) or skin involvement (T4b)
  • Nodal metastases occur frequently with breast carcinoma.
    • The axillary nodes are most commonly involved, with 10-40% of stage I and II malignancies showing pathological involvement of the axillary nodes at surgical resection
    • The internal thoracic nodes are also involved, usually when there are axillary metastases (20-50% risk with vs 0-10% risk without). The clinical significance of this nodal involvement is not clear.
  • Haematogenous metastases are most frequent to the skeleton, the lungs, the liver, and the brain. They can occur at many other sites.

Clinical Presentation

Many patients present with screen-detected disease and are otherwise asymptomatic. The other common group is those patients who self-detect a mass (more frequently women outside of the screening ages of 50-70).
Rare presentations include GP-detected mass, nipple discharge, Paget's disease of the breast, inflammatory breast cancer, or distant metastases (eg. brain metastases).
Examination findings can include:

  • Breast mass
    • May be firm and fixed with the more common ductal adenocarcinomas of no special type
    • May be less defined or non-palpable with lobular carcinoma
  • Axillary nodal disease
  • Peau d'orange skin changes
    • This occurs due to infiltration of the sub-dermal lymphatics, leading to lymphoedema of the overlying breast tissue.
  • Signs related to metastatic sites (eg. spine tenderness, neurological signs)

Imaging

Mammogram and ultrasound are the primary means of imaging breast cancers. MRI is increasing its role, particularly in women with dense breasts or lobular carcinoma.
The classical findings on mammogram and ultrasound are:

  • Spiculated, dense lesion
  • Microcalcifications from adjoining DCIS

Other types of breast carcinomas may have different features:

  • Medullary carcinomas often present as a dense, rounded mass
  • Lobular carcinomas may present as an indistinct mass that is not seen on the contralateral side

Tumour/Normal Tissue Features

The macroscopic and microscopic appearances of breast carcinomas vary according to their type, please see the links below.

Staging / Classification

All breast carcinomas are staged using the TNM system.

Tumour Stage

T1a: Tumour < 0.5 cm
T1b: Tumour 0.5 - 1 cm
T1c: Tumour 1 - 2 cm
T2: Tumour 2 - 5 cm
T3: Tumour > 5 cm with no involvement of skin or deep fascia
T4a: Tumour involves chest wall
T4b: Tumour involves the overlying skin
T4c: Involvement of skin and chest wall
T4d: Inflammatory Breast Carcinoma

Clinical Nodal Stage

N1: Mobile level I-II axillary nodes
N2a: Fixed level I-II axillary nodes
N2b: Involved internal thoracic nodes without axillary nodes
N3a: Involved level III axillary nodes
N3b: Involved internal thoracic with level I, II or III axillary nodes
N3c: Involved supraclavicular nodes

Pathological Nodal Stage

N1mi: Micro-metastases (< 2 mm size)
N
1a: Involvement of 1-3 level I or II axillary lymph nodes
N
1b: Pathologically involved internal thoracic nodes that were removed on sentinel lymph node biopsy
N
1c: Both N1a,, and N1b disease
N2a: Involvement of 4-9 level I or II axillary lymph nodes
N2b: Clinical involvement of internal thoracic nodes without pathological axillary nodal metastases
N3a: 10 or more axillary nodes involved or level III axillary node involvement
N3b: Clinical involvement of internal thoracic nodes with pathological axillary nodal metastases
N3c: Pathological involvement of supraclavicular lymph nodes

Distant Metastases

M0: No distant metastases
M1: Distant metastases

Overall Stage

Stage T N M
IA T1 N0 M0
IB T1 Nmi M0
IIA T1
T2
N1
N0
M0
IIB T2
T3
N1
N0
M0
IIIA T0-2
T3
N2
N1-2
M0
IIIB T4 N0-2 M0
IIIC TAny N3 M0
IV TAny NAny M1

Links