Test: Breast - 1 - NEET PG MCQ

• Breast assessment involves initial tissue sampling through FNAC.
• The most effective diagnostic method is biopsy, specifically FNAC True-cut (core-cut) biopsy.

• FNA is easily conducted but needs a skilled cytopathologist for precise interpretation of specimens.
• Core cutting needle biopsy yields a histological specimen that any pathologist can assess.
• False-negative results are frequently seen in fibrotic or well-differentiated tumours.
• Core biopsy specimens can routinely determine ER, PR status, and HER-2 overexpression.
• FNA is not reliable in differentiating invasive cancer from DCIS, which may result in overtreatment of substantial DCIS.
• It is the preferred diagnostic method for patients slated for preoperative systemic therapy.

• Biopsy Techniques for Breast Lesions:

• FNAC
  • Advantages: Quick, painless, and cost-effective.
  • No incision needed prior to selecting local therapy.
  • Disadvantages: Cannot differentiate between invasive and in situ cancer.
  • Markers (ER, PR, HER-2) are not typically available.
  • Requires an experienced cytopathologist.
  • There is a risk of false negatives and insufficient specimens.
• True-cut (core-cut) Biopsy
  • Advantages: Quick, relatively painless, and cost-effective. No incision needed.
  • Can be interpreted by any pathologist, with markers (ER, PR, HER-2) usually available.
  • Disadvantages: Possible false negatives and incomplete lesion characterisation.
• Excisional Biopsy
  • Advantages: Rare false negatives.
  • Provides complete histology before making treatment decisions.
  • May serve as a definitive lumpectomy.
  • Disadvantages: More costly and painful.
  • Involves an incision that will be part of definitive surgery.
  • May lead to unnecessary surgery and potential cosmetic deformity in patients with benign conditions.

Mammography continues to be more effective in identifying Ductal carcinoma in situ (DCIS). Screening using MRI outperforms mammography in spotting invasive breast cancer in younger women, as mammography's sensitivity is diminished due to the presence of dense breast tissue.

Despite mammography's superior sensitivity for identifying DCIS, it remains the preferred screening method for breast cancer because it can recognise microcalcifications, which are often the sole indication of DCIS. The sensitivity of ultrasound in detecting DCIS is considerably lower than that of mammography, making ultrasound a less effective screening tool for breast cancer. Additionally, MRI is unable to identify calcifications.

• Indications for Breast MRI include:
• Lobular carcinoma: This type is challenging to detect and assess using conventional methods due to its multifocal and infiltrative growth pattern.
• Staging of primary breast cancer.
• Occult primary tumours associated with malignant axillary lymphadenopathy, where mammograms and breast ultrasounds appear normal.
• Screening younger women who have a significantly elevated familial risk of breast cancer.
• Evaluating the integrity of breast implants.

• Mammography delivers a radiation dose of 0.1 cGy for each study (chest radiography provides 25% of this dose).
• No increased risk of breast cancer is associated with the radiation dose from screening mammography.
• It is employed to identify unexpected breast cancer in women without symptoms.
• Two views of the breast are captured: the craniocaudal view and the mediolateral oblique view.
• The MLO view captures the largest volume of breast tissue, including the upper outer quadrant and axillary tail of Spence.
• The CC view offers improved visibility of the medial side of the breast and allows greater breast compression.
• Mammography is also utilised to assist in interventional procedures, such as needle localisation and needle biopsy.
• Sensitivity significantly decreases in younger or denser breasts and is deemed unsuitable for patients under 35 years.

• Mammographic features indicative of breast cancer include:
• A solid mass with or without stellate characteristics.
• Asymmetric thickening of breast tissues.
• Clustered microcalcifications.
• The presence of fine, stippled calcium surrounding a suspicious lesion, which is suggestive of breast cancer and can occur in up to 50% of nonpalpable cancers.
• These microcalcifications are particularly significant in younger women, where they may represent the only mammographic abnormality.

• Advantages of mammography include:
• A reduction in mortality by approximately 33% for women following screening mammography.
• Mammography is more accurate than clinical examination for detecting early breast cancers, yielding a true-positive rate of 90%.
• From the age of 40, women should undergo yearly breast examinations and have an annual mammogram.
• Mammography contributes to a 40% decrease in stage II, III, and IV cancers within the screened population, along with a 30% increase in overall survival.

• BIRADS (Breast Imaging Reporting And Data System) Category Definition
• 0: Assessment incomplete; further imaging evaluation required.
• 1: Negative result; a routine mammogram is advised in one year.
• 2: Findings are benign; a routine mammogram is recommended in one year.
• 3: Probably benign findings; short-term follow-up is suggested.
• 4: Abnormality is suspicious; a biopsy should be considered.
• 5: Highly indicative of malignancy; appropriate measures should be taken.
• 6: Malignancy confirmed by biopsy.

• Calcification patterns in breast diseases include:
• Carcinoma: Microcalcification, characterised by punctate and branching formations.
• Fibroadenoma: Exhibits a popcorn-like appearance, which is coarse, granular, and resembles crushed stones.
• Fibrocystic disease: Demonstrates a powdery texture.
• Fat necrosis: Typically shows a curvilinear pattern.

Risk Factors for breast cancer include:

• Age: The likelihood of developing breast cancer rises with age.
• Country of birth: The disease is more prevalent in western nations.
• Family history and genetic predispositions (e.g., BRCA mutations).
• Hyperestrogenemia:
  • Early onset of menstruation and late menopause.
  • Nulliparity (never having given birth).
  • Obesity.
• Having a late first full-term pregnancy.
• Alcohol consumption and a diet high in fats.
• Personal history of malignancy:
  • Contralateral breast cancer.
  • Ovarian and endometrial cancers.
• Previous benign breast diseases.
• High socioeconomic status.
• Radiation exposure.
• Hormone replacement therapy:
  • Combined therapy (estrogen + progesterone) is linked to a higher risk of breast cancer.
  • Estrogen-only therapy does not appear to increase the risk.
• Smoking and oral contraceptive pills (OCPs) do not seem to elevate the risk of breast cancer.
• A longer duration of breastfeeding is associated with a protective effect.

• Proliferative Lesions Relative Risks for developing invasive breast cancer
• Nonproliferative changes: 70% Relative Risk = 1.0
  • Adenosis
  • Cysts and apocrine change
  • Ductal ectasia
  • Mild epithelial hyperplasia of usual type
• Proliferative disease without atypia: 26% Relative Risk = 1.5–2.0
  • Hyperplasia of usual type, moderate or florid
  • Papilloma
  • Sclerosing adenosis
• Proliferative disease with atypia: 4% Relative Risk = 4–5
  • Atypical ductal hyperplasia
  • Atypical lobular hyperplasia

Cancer Risk Associated with Benign Breast Disorders and In Situ Carcinoma of the Breast

• Abnormality Relative Risk
• Nonproliferative lesions of the breast: No increased risk
• Sclerosing adenosis: No increased risk
• Intraductal papilloma: No increased risk
• Florid hyperplasia: 1.5 to 2-fold
• Atypical lobular hyperplasia: 4-fold
• Atypical ductal hyperplasia: 4-fold
• Ductal involvement by cells of atypical ductal hyperplasia: 7-fold
• Lobular carcinoma in situ: 10-fold
• Ductal carcinoma in situ: 10-fold

Harrison states that “Women who inherit a mutated allele of the BRCA-1 gene from either parent have a minimum of a 60–80% lifetime probability of developing breast cancer and approximately a 33% chance of developing ovarian cancer.” Schwartz remarks that “Germline mutations in BRCA1 are a predisposing genetic factor in as much as 45% of hereditary breast cancers and in at least 80% of hereditary ovarian cancers. Female carriers of the mutation face up to a 90% lifetime risk of developing breast cancer and a risk of up to 40% for ovarian cancer.”

• BRCA-1 Chromosome: 17
• BRCA-2 Chromosome: 13

BRCA-1 associated breast cancers:

• Invasive ductal carcinomas
• Poorly differentiated
• Hormone-receptor negative
• Early age of onset
• Bilateral

BRCA-2 associated cancers:

• Invasive ductal carcinomas
• Well differentiated
• Hormone-receptor positive
• Early age of onset
• Bilateral

Associated cancers include ovarian, colon, and prostate cancers for BRCA-1, while BRCA-2 is linked to ovarian, colon, prostate, pancreas, gall bladder, stomach cancers, and melanoma.

Carcinoma Breast Risk Assessment Models

• Gail Model
• Claus Model

These are the most commonly utilised models:

• Factors considered include:
• Age at menarche
• Number of breast biopsies
• Age at first live birth
• Number of first-degree relatives with breast cancer
• The models predict the cumulative risk of breast cancer based on the decade of life.
• They are founded on assumptions regarding the prevalence of high-penetrance breast cancer susceptibility genes.
• While the models include more detailed family history information, they omit other risk factors.
• Risk estimates for breast cancer are determined by:
• Decade of life
• Presence of 1st and 2nd-degree relatives diagnosed with breast cancer
• Age at diagnosis of those relatives
• Factors that are less reliably linked to breast cancer, such as diet, use of oral contraceptive pills (OCPs), and lactation, are excluded.
• Additionally, rare factors in the general population, like radiation exposure, are not incorporated into the Gail or Claus models.

None of these models consider the risk associated with mutations in BRCA1 and BRCA2.

Incidence of sporadic, familial, and hereditary breast cancer:

• Sporadic breast cancer: 65-75%
• Familial breast cancer: 20-30%
• Hereditary breast cancer: 5-10%

• BRCA1: 45%
• BRCA2: 35%
• p53 (Li-Fraumeni syndrome): 1%
• STK11/LKB1 (Peutz-Jeghers syndrome): <1%
• PTEN (Cowden disease): <1%
• MSH2/MLH1 (Muir-Torre syndrome): <1%
• ATM (Ataxia-telangiectasia): <1%
• Unknown: 20%

Hereditary breast cancer includes:

• BRCA and PLACH: PJS, Li-Fraumeni, Ataxia telangiectasia, Cowden’s, HNPCC

Fibrocystic change does not result in breast carcinoma. According to Robbins, “Fibrocystic changes (Non-proliferative breast changes): Non-proliferative changes are most probably a component of the range of histological characteristics that can be seen in normal breast tissue.”

DCIS (Ductal carcinoma in situ) constitutes nearly half of the cancers identified through mammography. It typically appears as calcifications on mammograms. The histological classifications of DCIS include five distinct types:

• Comedocarcinoma
• Cribiform
• Micropapillary
• Solid
• Papillary

The types are further categorised by grade:

• Low Grade: Cribiform, Papillary, and Micropapillary
• High Grade: Solid and Comedocarcinoma

Lymphatic metastasis in breast cancer occurs via the subareolar lymphatic plexus of Sappey, as well as through cutaneous and inflammatory lymphatics. The primary sites for lymphatic spread are:

• Axillary lymph nodes (75%)
• Internal mammary lymph nodes

Tumours located in the posterior third of the breast have a higher likelihood of draining to the internal mammary nodes. The involvement of lymph nodes holds both biological and chronological importance:

• It signifies an evolutionary step in the carcinoma's spread.
• It serves as an indicator of the tumour's metastatic potential.

The presence of supraclavicular nodes and any contralateral lymph nodes indicates advanced disease. Lymph node metastasis is typically addressed through surgical dissection or radiotherapy.

Inflammatory carcinoma is a concerning clinical category linked with widespread tumour involvement of the lymphatic channels in the breast and the skin above it.

• WHO Classification of Breast Cancer:
• In-situ Carcinoma
• Invasive Carcinoma (MC)
• Paget’s Disease of the Nipple
• Ductal carcinoma in-situ
• Lobular carcinoma in-situ
• Ductal carcinoma (MC)
• Lobular carcinoma
• Tubular (Cribiform) carcinoma
• Mucinous (Colloid) carcinoma
• Medullary carcinoma
• Papillary carcinoma
• Metaplastic carcinoma
• Inflammatory carcinoma

Invasive Breast Carcinoma includes invasive ductal carcinoma, which is responsible for 80% of breast cancers. It may present with:

• Macroscopic or microscopic axillary LN metastases in up to 60% of instances.
• Typically occurs in perimenopausal or postmenopausal women in their 5th to 6th decades of life.
• Appears as a solitary, firm mass.

Medullary Carcinoma is a special type of breast cancer that constitutes 4% of all invasive breast cancers. It is characterised by:

• A frequent phenotype of BRCA-1 hereditary breast cancer.
• A gross appearance that is soft and haemorrhagic.
• A potential rapid increase in size due to necrosis and haemorrhage.
• A bulky nature, often situated deep within the breast.

Microscopically, it shows:

• A dense lymphoreticular infiltrate of lymphocytes and plasma cells.
• Large pleomorphic nuclei.
• A sheet-like growth pattern.

It has a better 5-year survival rate compared to those with NST or invasive lobular carcinoma.

Mucinous Carcinoma (Colloid Carcinoma) accounts for 2% of all invasive breast cancers and typically:

• Presents in elderly individuals as a bulky tumour.
• Is characterised by extracellular pools of mucin.
• Requires analysis of multiple sections for a conclusive diagnosis.
• Shows LN metastases in 33% of cases, with 5- and 10-year survival rates of 73% and 59%, respectively.

Papillary Carcinoma is another special type, making up 2% of all invasive breast cancers. It:

• Presents in the 7th decade of life and is more prevalent among nonwhite women.
• Is typically small, rarely exceeding 3 cm in diameter.
• Is defined by papillae with fibrovascular stalks and multilayered epithelium.
• Exhibits a low frequency of axillary LN metastases.
• Has 5- and 10-year survival rates akin to those for mucinous and tubular carcinoma.

Tubular Carcinoma, another special type, constitutes 2% of all invasive breast cancers and is usually diagnosed during the perimenopausal or early menopausal phases. Distant metastases are uncommon, with long-term survival approaching 100%.

Invasive Lobular Carcinoma represents 10% of breast cancers. This type is often multifocal, multicentric, and bilateral.

The lumbar vertebrae are the most frequent site for metastasis originating from breast carcinoma. According to Bailey, “Skeletal metastases arise through this pathway (dissemination via the bloodstream), although the initial spread can occur through the lymphatic system. In terms of frequency, the affected sites include:

• lumbar vertebrae
• femur
• thoracic vertebrae
• ribs
• skull

These metastatic deposits are typically osteolytic.

• Upper inner (12–15%)
• Upper outer (approximately 50%)
• Lower inner (3–5%)
• Lower outer (6–10%)
• Central/areolar (20%)

Retraction of the nipple occurs as a result of fibrosis in and around the subareolar duct.

Retraction or dimpling of the skin is caused by the involvement of Cooper's ligament.

Peau d'orange is the result of obstruction in the subdermal lymphatics.

The Van Nuys Prognostic Index (VNPI) is extensively utilised to categorise ductal carcinoma in situ (DCIS) into various risk groups that can be managed accordingly. Efforts have been made to pinpoint subsets of DCIS for which wide excision without radiotherapy would ensure adequate local control.

• Silverstein and colleagues developed the Van Nuys criteria from a cohort of DCIS patients who underwent wide excision, both with and without radiation therapy.
• They proposed a system to determine which patients could forgo radiation therapy based on:
• The patient’s age
• The nuclear grade of DCIS and the existence of microcalcification
• The size of the lesion
• The width of the surgical margin

Chest wall involvement refers to the engagement of:

• Ribs
• Intercostal muscles
• Serratus anterior

These structures constitute the chest wall, rather than the pectoralis major.

Types of Mastectomy:

• Simple or Total Mastectomy: Involves the excision of breast tissue, the nipple-areola complex, and skin.
• Extended Simple Mastectomy: Includes simple mastectomy along with the removal of level I axillary lymph nodes (LNs).
• Modified Radical Mastectomy: Entails the removal of all breast tissue, the nipple-areola complex, skin, and both level I and II axillary LNs.
• Halstead’s Radical Mastectomy: Involves the extraction of all breast tissue, skin, nipple-areola complex, pectoralis major and minor muscles, as well as level I, II, and III axillary LNs.
• Extended Radical Mastectomy: A radical mastectomy that also includes the removal of internal mammary LNs.
• Super Radical Mastectomy: A radical mastectomy that incorporates the removal of internal mammary, mediastinal, and supraclavicular LNs.

• Variants of Modified Radical Mastectomy (MRM):
• Auschincloss Procedure: Removes all breast tissue, the nipple-areola complex, skin, and level I and II axillary LNs.
• Patey’s Procedure: Involves the removal of the pectoralis minor to facilitate complete dissection of level III axillary LNs.
• Scanlon’s Modification of Patey’s Procedure: Instead of removing the pectoralis minor, it is divided, allowing for complete excision of level III axillary LNs.

• Axillary LN Levels in Relation to Pectoralis Minor:
• Level I: Located below or lateral to the pectoralis minor; includes anterior, posterior, and lateral axillary LNs.
• Level II: Found posterior (behind) the pectoralis minor; encompasses central and interpectoral axillary LNs.
• Level III: Positioned medial or above the pectoralis minor; consists of apical axillary LNs.