Breast cancer

Classification

Molecular Subtypes

• Luminal A: A Luminal A carcinoma is hormone receptor-positive, HER2-negative, well-differentiated with a low Ki-67.
• Luminal B: A Luminal B carcinoma is hormone receptor-positive with a high Ki-67 or poorer grade, HER2 negative or positive.
• Triple-negative: In triple-negative breast cancer: oestrogen receptor, progesterone receptor, and HER2 are all negative.

Aetiopathogenesis

BRCA and HRD

• BRCA1/2 function: BRCA1 and BRCA2 are tumour suppressor genes involved in homologous recombination, which repair DNA double-strand breaks.
• HRD definition: HRD means homologous recombination deficiency, i.e., the functional defect of this repair pathway even without a BRCA mutation.
• Germline vs. somatic mutation: A germline mutation differs from a somatic mutation in that it is present in all body cells and can be inherited.

Clinical features

History

• Regarding the finding itself, questions are asked about duration, change in size, pain, cyclical nature, and nipple discharge.
• The family history records breast and ovarian cancers in relatives and their respective age at diagnosis.
• The age of affected relatives at diagnosis is important because it is part of the score for indicating BRCA testing.

Inspection

• In a sitting position, with arms lowered and raised, one looks for asymmetry, bulging, plateau sign, skin dimpling, and nipple retraction.
• Peau d'orange is caused by lymphatic congestion in the cutis, which tethers the skin at the hair follicles.

Palpation

• Technically, one palpates flat with the finger pads against a counter-pressure, systematically in all quadrants, in sitting and supine positions.
• A lump typical of carcinoma is firm, poorly defined, has limited mobility, and is mostly painless.
• Also palpated are the axilla as well as the infraclavicular and supraclavicular regions bilaterally.
• The most common location is the upper outer quadrant, accounting for about half of all carcinomas.

More facts from the study questions

• The typical palpation findings of a breast carcinoma are a firm consistency, poor demarcation from surrounding tissue and low mobility.
• The correct sequence is: mammography before core needle biopsy.
• A haematoma caused by the biopsy can significantly impair the interpretability of a subsequent mammogram.
• After a suspicious palpable finding, ultrasound of both breasts and the axillae is the first imaging step.
• It serves to further characterise the finding.
• Approximately half of all breast carcinomas are located in the upper outer quadrant.
• This area is examined with particular care during palpation.
• An eczematous, scaly, erosive change of the nipple is suspicious for Paget's disease of the nipple.
• The Elston and Ellis grading system is an established system for assessing the aggressiveness of breast carcinoma.
• It is based on the histological evaluation of three criteria: tubule formation, nuclear pleomorphism and mitotic rate.

Histology

Mandatory Information

• Histological type: The pathology report first states the histological type, i.e. invasive, no special type (NST), invasive lobular, or a special type.
• Grading according to Elston and Ellis: This assesses the three criteria of tubule formation, nuclear pleomorphism, and mitotic rate.
• Hormone receptor status: This includes the oestrogen and progesterone receptor status as a percentage of stained tumour cell nuclei.
• HER2 status: The HER2 status is determined by immunohistochemistry and re-tested by FISH if 2+.
• Ki-67: The proliferation marker Ki-67 measures the proportion of proliferating cells and thus the growth rate.

Diagnosis

Five malignant signs

• Shape: A carcinoma is typically irregular, angular or spiculated.
• Orientation: The orientation of a malignant lesion to the skin is mostly vertical, i.e., taller-than-wide.
• Internal echoes: The internal echoes of a carcinoma are characteristically markedly hypoechoic and inhomogeneous.
• Posterior phenomenon: Posterior to the lesion, there is often an acoustic shadow because the tumour is sound-absorbing and desmoplastic.
• Surroundings: The surroundings of a carcinoma show an echogenic halo and infiltration instead of displacement.

Axilla and Doppler

• Normal lymph node: An unremarkable axillary lymph node has a broad, echogenic fatty hilum and a narrow, hypoechoic cortex.
• Lymph node suspicious for malignancy: A lymph node is suspicious for malignancy if it is round, shows an effaced hilum and an eccentrically thickened cortex.
• Colour Doppler: In carcinoma, Colour Doppler often shows prominent, irregularly penetrating peripheral vessels, but is not conclusive on its own.

Limitations of Ultrasound

• Necessity of mammography: Mammography remains indispensable because ultrasound does not reliably detect microcalcifications and thus DCIS.
• Difficult to detect on mammography: Often difficult to detect on mammography are lobular carcinomas and LCIS, because they grow diffusely and show little density difference.

What the abbreviations stand for

• BI-RADS stands for Breast Imaging Reporting and Data System of the American College of Radiology.
• ACR in this context stands for the American College of Radiology, which defines density categories a to d.

Categories

• BI-RADS 0 means assessment incomplete, further imaging or prior images are needed.
• BI-RADS 4 means suspicious, subdivided into 4a to 4c — histological clarification required.

Density

• ACR a and b describe predominantly fatty involuted glandular tissue with good mammographic assessability.
• ACR c and d describe dense glandular tissue where the sensitivity of mammography is reduced.
• In practice, high density means a higher risk of interval cancer and the importance of supplementary ultrasound.

Typical imaging findings

• Ultrasound: The hypoechoic lesion stands perpendicular to the skin and is larger in depth than in width. Its margins are ill-defined and the internal structure heterogeneous; the calipers show the vertical diameter to be the larger one.
• Ultrasound: The lesion is hypoechoic with ill-defined, angular margins and a heterogeneous internal structure. Marked posterior shadowing is seen behind it; the surrounding tissue planes appear interrupted and calipers span the lesion.
• Mammography: Fine strands of differing length radiate in a stellate pattern from a dense centre into the surrounding tissue. The normal connective tissue strands are pulled towards this point; the lesion has no smooth margin and no bright halo.
• Mammography: On the right there is a dense, irregularly bordered mass with fine spicules radiating into the surrounding tissue in a stellate fashion. The left side is normal by comparison; no microcalcification is visible within the lesion.

Keep learning in the app

Further reading (selection)

1. StatPearls: Breast Cancer (NCBI Bookshelf)
2. German Guideline Program in Oncology: S3 guideline on breast cancer (German)
3. DocCheck Flexikon, Mammakarzinom
4. DocCheck Flexikon, Mammasonographie
5. DocCheck Flexikon, BI-RADS
6. DocCheck Flexikon, BRCA1

Cross-references