Invasive Breast Cancer

Introduction

Carcinoma of the breast is the most common cancer in the Western world and accounts for 20% of all cancers in women in the UK, with 1 in 10 women developing breast cancer in their lifetime (the prevalence of the condition in males is significantly less)

Fig. 1 – macroscopic appearance of breast carcinoma, following simple mastectomy

Invasive carcinoma of the breast can be classified into:

  • Invasive ductal carcinoma (75-85%)
  • Invasive lobular carcinoma (10%)
  • Other subtypes (5%)
    • Examples include medullary carcinoma or colloid carcinoma

Historically, ductal and lobular carcinomas were originally divided on the basis that ductal carcinomas arise in the ducts and lobular carcinomas arise in the lobules; it is now known that almost all breast carcinomas actually arise in the terminal duct lobular unit but this classification remains in use due to the different behaviour of the two subtypes.

Breast Screening Programmes

In the UK, the NHS breast cancer screening programme currently invites women aged 50-70 to have a mammogram every three years; any abnormalities identified will be referred to breast clinic for the triple assessment.

Classification

Invasive Ductal Carcinoma

Invasive ductal carcinoma (IDC) is the most common type of breast carcinoma, constituting 80% of all cases.

IDCs can be further classified into tubular, cribriform, papillary, mucinous (/colloid), or medullary carcinomas, all showing distinct patterns of growth*.

*Tubular, cribriform and papillary subtypes are well circumscribed and show the most favorable prognoses.

Invasive Lobular Carcinoma

Invasive lobular carcinoma (ILC) is the second most common type of breast cancer, constituting 10% of all invasive breast cancers. ILC is more common in older women.

It is characterised by a diffuse (stromal) pattern of spread that makes detection more difficult. By the time of diagnosis, tumours are often quite large.

Fig. 2 – Histology of (A) Invasive Ductal Carcinoma (B) Invasive Lobular Carcinoma


Risk Factors

Female sex and age are the most significant risk factors for breast cancer, with the risk of breast cancer doubling every ten years until the menopause.

Mutations to certain genes are well-documented risk factors, most importantly the tumour suppressor genes BRCA1 and BRCA2.

Family history in a first degree relative*, previous benign disease, obesity, alcohol consumption, and geographic variation (more common in developed countries) are all significant risk factors for breast malignancy.

*1.5-2 times increase if one relative, 4-6 times increase if two affected relatives

Degree of exposure to unopposed oestrogen has also been well-documented to cause an increase in risk to develop breast cancer. Factors that influence this include early menarche, late menopause, nulliparous women, first pregnancy after 30 years of age, and oral contraceptives or HRT


Clinical Features

Patients can present symptomatically or asymptomatically via screening (particularly for ILC). Symptoms may include breast lump(s), asymmetry, or swelling (all or part of breast), abnormal nipple discharge, nipple retraction, skin changes (dimpling/peau d’orange, or Paget’s-like changes), mastalgia, or with a palpable lump in the axilla.


Differential Diagnosis

All suspected breast cancers should be referred for a triple assessment, where the definitive diagnosis can be obtained.

Benign tumours, breast cysts, or infective causes are all potential differentials, yet majority of which are identified following suitable imaging and histology.


Investigations and Management

The current gold standard for diagnosis of breast lumps is via the triple assessment, involving examination, imaging, and histology/cytology.

Management for breast malignancies is extensive and variable, and is explained more here.


Prognosis

Overall, nodal status is the single most important prognostic factor in breast cancer, however size, grade, and receptor status also influence prognosis.

The Nottingham Prognostic Index (NPI) is a widely used clinicopathological staging system for primary breast cancer prognosis. It is calculated by:

(Size x 0.2) + Nodal Status + Grade

Size is the diameter of the lesion in cm, nodal status is number of axillary lymph nodes involved (0 nodes=1, 1-4 nodes=2, >4 nodes=3), and grade is based on Bloom-Richardson classification

Score 5 Year Survival
≥2.0 and ≤2.4 93%
>2.4 and ≤3.4 85%
>3.4 and ≤5.4 70%
>5.4 50%

 

N.b. Importantly, this data was first published in 1992 and a variety of other factors, outside of the NPI, such as vascular invasion and receptor status, are now also used in prognostics.

Due to potential new targeted therapies, receptor status is now a key feature in determining mortality rates. All breast malignancies should be checked for their Oestrogen Receptor (ER), Progesterone Receptor (PR), and Human Epidermal growth factor Receptor (HER2) status, allowing for suitable treatment options to be developed.


Paget’s Disease of the Nipple

Paget’s disease of the nipple is a rare condition presents as a roughening, reddening, and slight ulceration of the nipple. The vast majority of Paget’s (97%) will also have an underlying neoplasm, either in situ or invasive disease, and it is associated with 1-4% of all cases of breast cancer.

Microscopically there is involvement of the epidermis by malignant ductal carcinoma cells. The mechanism behind Paget’s disease is currently unknown, however it is hypothesized that either malignant cells migrate from the ducts to the nipple surface or the cells of the nipple themselves become malignant

Clinical Presentation

Clinical features of Paget’s disease of the nipple include an itching or redness in the nipple and/or areola, with flaking and thickened skin on or around the nipple

The area is often painful and sensitive. A flattened nipple, with or without yellowish or bloody discharge, may also be indicative of the disease.

Fig. 3 – Pagets Disease of the Nipple, involving the areola and the nipple

Differential Diagnosis

Due to its involvement of the skin of the nipple, Paget’s disease of the breast is often mistaken for dermatitis or eczema.

Paget’s disease can be differentiated from eczema on the basis that the former always affects the nipple and only involves the areola as a secondary event, whilst eczema nearly always only involves the areola and spares the nipple.

Investigations

A biopsy is needed to confirm diagnosis; in certain cases, the entire nipple may be removed for histological examination.

Given its association with malignancy, a full breast and axilla examination should also be performed. Mammograms, ultrasounds, or MRI breast may also be considered.

Management

First line management of Paget’s disease is surgical.  The type of surgery depends on how advanced the underlying breast cancer is, but in all cases the nipple and areola will be removed.

In the cases associated with an underlying malignancy, radiotherapy may also be necessary.

Quiz

Question 1 / 5
How does ductal carcinoma in situ most commonly present?

Quiz

Question 2 / 5
Of the following patients, who has the highest risk for invasive ductal carcinoma?

Quiz

Question 3 / 5
Which of the following is not a risk factor for invasive ductal carcinoma?

Quiz

Question 4 / 5
A 58 year old woman is confirmed to have invasive ductal carcinoma on tissue biopsy pathology. In consultation with her physicians, she makes it clear that she is opposed to getting radiation therapy, for fear of side effects. What is the most appropriate treatment option for this patient?

Quiz

Question 5 / 5
Which of the following statements is true about a patient found to have non-invasive lesion in the lobules and terminal ducts of the right breast?

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