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Questions and Answers
What role do metabolites of oestrogen play in the development of breast cancer?
What role do metabolites of oestrogen play in the development of breast cancer?
Which statement accurately describes the risk associated with BRCA1 gene mutations?
Which statement accurately describes the risk associated with BRCA1 gene mutations?
Which metabolite of oestrogen is considered protective against breast cancer?
Which metabolite of oestrogen is considered protective against breast cancer?
What condition is associated with Li-Fraumeni syndrome?
What condition is associated with Li-Fraumeni syndrome?
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What indicates a possible familial syndrome in breast cancer cases?
What indicates a possible familial syndrome in breast cancer cases?
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What is considered the most significant risk factor for the development of breast carcinoma?
What is considered the most significant risk factor for the development of breast carcinoma?
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Which age group accounts for 70% of breast carcinoma cases in females?
Which age group accounts for 70% of breast carcinoma cases in females?
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Which factor is NOT associated with an increased risk of breast cancer?
Which factor is NOT associated with an increased risk of breast cancer?
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What is the lifetime risk of developing breast carcinoma for females?
What is the lifetime risk of developing breast carcinoma for females?
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What effect does atypical ductal hyperplasia have on breast cancer risk?
What effect does atypical ductal hyperplasia have on breast cancer risk?
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How does hormone replacement therapy affect breast cancer risk?
How does hormone replacement therapy affect breast cancer risk?
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Which of the following is a known protective factor against breast cancer?
Which of the following is a known protective factor against breast cancer?
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Which type of breast cancer is characterized as the most common non-skin cancer in females?
Which type of breast cancer is characterized as the most common non-skin cancer in females?
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Which of these factors is NOT directly associated with the protective effect of pregnancy and lactation against breast cancer?
Which of these factors is NOT directly associated with the protective effect of pregnancy and lactation against breast cancer?
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According to the provided text, what is the relative risk increase per year of hormone replacement therapy (HRT) treatment for developing breast cancer?
According to the provided text, what is the relative risk increase per year of hormone replacement therapy (HRT) treatment for developing breast cancer?
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Based on the text, which statement accurately describes the relative risk associated with atypical epithelial hyperplasia?
Based on the text, which statement accurately describes the relative risk associated with atypical epithelial hyperplasia?
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Which of the following is NOT considered a risk factor for developing breast carcinoma, as presented in the provided text?
Which of the following is NOT considered a risk factor for developing breast carcinoma, as presented in the provided text?
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If an individual migrating to a new country adopts the dietary patterns of that country, which aspect of breast cancer risk does this primarily relate to?
If an individual migrating to a new country adopts the dietary patterns of that country, which aspect of breast cancer risk does this primarily relate to?
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Which of the following statements best describes the relationship between breast cancer and genetics?
Which of the following statements best describes the relationship between breast cancer and genetics?
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Based on the text, what is the key difference between hormonal-sporadic and genetic-hereditary breast cancer?
Based on the text, what is the key difference between hormonal-sporadic and genetic-hereditary breast cancer?
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Which of the following statements best reflects the information the text provides regarding the epidemiology of breast cancer?
Which of the following statements best reflects the information the text provides regarding the epidemiology of breast cancer?
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Which statement accurately describes the relationship between oestrogen metabolites and breast cancer?
Which statement accurately describes the relationship between oestrogen metabolites and breast cancer?
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The presence of which of the following factors in a family history would NOT significantly suggest a familial breast cancer syndrome?
The presence of which of the following factors in a family history would NOT significantly suggest a familial breast cancer syndrome?
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Which of the following genetic mutations is NOT directly linked to an increased risk of breast cancer?
Which of the following genetic mutations is NOT directly linked to an increased risk of breast cancer?
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Which statement best describes the typical breast cancer characteristics associated with BRCA1 gene mutations?
Which statement best describes the typical breast cancer characteristics associated with BRCA1 gene mutations?
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Which of the following statements regarding the use of oral contraceptive pills (OCPs) and breast cancer risk is MOST accurate?
Which of the following statements regarding the use of oral contraceptive pills (OCPs) and breast cancer risk is MOST accurate?
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Flashcards
Oestrogen and Breast Cancer Risk
Oestrogen and Breast Cancer Risk
Oestrogen increases the risk of breast cancer by promoting cell proliferation.
Metabolites of Oestrogen
Metabolites of Oestrogen
Oestrogen is metabolized into derivatives like 2-OHE1 and 16α-OHE1.
BRCA1
BRCA1
A gene linked to a high risk of breast and ovarian cancers; carriers may also face risks for other cancers.
BRCA2
BRCA2
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Signs of Hereditary Breast Cancer
Signs of Hereditary Breast Cancer
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Malignant Breast Disease
Malignant Breast Disease
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Incidence of Breast Cancer
Incidence of Breast Cancer
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Risk Factors
Risk Factors
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Protective Effects
Protective Effects
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Genetic Factors
Genetic Factors
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Hormonal Factors
Hormonal Factors
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Reproductive History
Reproductive History
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Atypical Hyperplasia
Atypical Hyperplasia
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Breast Carcinoma
Breast Carcinoma
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Lifetime Risk of Breast Cancer
Lifetime Risk of Breast Cancer
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Major Risk Factors
Major Risk Factors
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Age and Breast Cancer
Age and Breast Cancer
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Radiation Exposure
Radiation Exposure
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Pregnancy Effects
Pregnancy Effects
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Hormonal Treatment Impact
Hormonal Treatment Impact
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Atypical Epithelial Hyperplasia
Atypical Epithelial Hyperplasia
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Oestrogen Mechanism
Oestrogen Mechanism
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2-Hydroxyestrone (2-OHE1)
2-Hydroxyestrone (2-OHE1)
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16α-Hydroxyestrone (16α-OHE1)
16α-Hydroxyestrone (16α-OHE1)
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Li-Fraumeni Syndrome
Li-Fraumeni Syndrome
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PTEN Cowden Disease
PTEN Cowden Disease
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Study Notes
Malignant Breast Disease
- Class: Year 2
- Course: Pathology
- Lecturer: Prof Paul Murray
- Date: February 2024
Learning Objectives
- List and discuss malignant breast disease
- Describe the epidemiology of breast cancer (including risk factors)
- List different types of breast cancers
- Discuss the prognosis of breast cancer
- Discuss the management of breast cancer
Breast Carcinoma
-
Most common non-skin cancer in females
-
Second most common cause of cancer mortality in females
-
Incidence is increasing
-
Lifetime risk is 1 in 9
-
Aetiology unknown: Major risk factors include excess estrogen and genetic factors
Risk Factors for Breast Carcinoma
- Female gender: 70% of cases in females over 50
- Increasing age: Breast cancer incidence increases with age.
- Early menarche and late menopause: Early menarche and late menopause may increase the risk.
- Nulliparity and first birth after 35: Women who have not had children or whose first child is born after 35 years of age may have a higher risk.
- Radiation exposure: Exposure to radiation may increase the risk.
- Post-menopausal obesity: Post-menopausal obesity may increase the risk.
- Pregnancy and lactation: Pregnancy and lactation have a protective effect against breast cancer.
- Dietary fat: Dietary fat may be a risk factor.
- Alcohol: Alcohol consumption may increase the risk.
- Race: Differences in breast cancer incidence exist across races. Geographic influence: Migrants tend to adopt the pattern of the host country.
- Exposure to estrogen: Exposure to estrogen may increase the risk.
- Genetics: Genetic factors play a role in breast cancer development.
Risk Factors (Race and Ethnicity)
- Breast Cancer Incidence in U.S. Women (2015-2019): Data displayed in a graph showing incidence rates among different racial and ethnic groups.
Risk Factors (Other)
- Carcinoma of the contra-lateral breast or endometrium
- Atypical epithelial hyperplasia: 1.5-2x relative risk for usual hyperplasia, 4-5x relative risk for atypical ductal hyperplasia; Double relative risk with positive family history
- Family History: Double relative risk with positive family history
Aetiology and Pathogenesis
- Hormonal (sporadic)
- Genetics (hereditary)
Breast Histology
- Anatomy of the breast including the duct, interlobular stroma, lobule, intralobular stroma, acini, basement membrane, myoepithelial cells, luminal epithelial cells, lumen (with eosinophilic secretions). Images of breast tissue sections are provided.
Hormonal-Sporadic
- Age at menarche and menopause.
- Reproductive history
- Breastfeeding(protective)
- Exogenous oestrogens
- Hormone replacement therapy: Relative risk increases by 1.02/year of treatment. Risk persists for 5 years after cessation. Type of preparation important (e.g. type of progestogen). Oral contraceptive pills or the injectable contraceptive depo-Provera – very small increased risk.
Oestrogen Increases Breast Cancer Risk
- Oestrogen → proliferation of pre-malignant lesions and cancers
- Metabolites of oestrogen: 2-hydroxyestrone (2-OHE1) is considered protective, 16α-hydroxyestrone (16a-OHE1) promotes growth and proliferation.
Hereditary Breast Cancer
- BRCA1: High risk of ovarian cancer, susceptible to other cancers (colon, prostate, pancreas), Breast cancers tend to have medullary features (ER-, Her2-), Difficult to visualize on mammogram.
- BRCA2: Higher risk of male breast cancer, susceptible to other cancers (colon, prostate, pancreas), Breast cancers more similar to sporadic cancers, Visible on mammogram.
- TP53 Li-Fraumeni syndrome, PTEN Cowden disease
Genetic Factors-Hereditary Breast Cancer
- Suspect familial syndrome if:
- Multiple first-degree relatives with breast carcinoma
- Tumour at pre-menopausal age (less than 40)
- Multiple tumours
- Bilateral breast cancer
- Breast and ovarian cancer
- Male breast cancer
- Breast cancer <40 yrs
- Multiple first-degree relatives with breast cancer.
Cell of Origin
- Most cancers are ER positive.
- Originate from ER expressing luminal cells.
- Precursor lesions are ER positive.
- ER negative tumours, Myoepithelial cells or OR ER positive luminal cells that lose ER expression.
- Unknown precursor
Classification of Breast Cancer
- Non-invasive (carcinoma in situ): Tumour cells confined to epithelium and have not penetrated basement membrane.
- Ductal carcinoma in situ (DCIS): Architectural subtypes include comedo, solid, cribriform, papillary, and micropapillary.
- Lobular carcinoma in situ (LCIS)
- Invasive: Tumour cells have penetrated basement membrane and invaded stroma
Ductal Carcinoma In Situ (DCIS)
- Increased incidence of DCIS
- Mammography, increasing age, lifestyle
- DCIS often found in association with invasive cancers
- Precursor lesions of invasive cancers
- Management: Wide local excision, +/- radiotherapy, Mastectomy, Chemoprevention (Tamoxifen)
Ductal Carcinoma In Situ (DCIS): Architectural Subtypes
- Architectural subtypes (comedo, solid, cribriform, papillary, micropapillary)
- Risk of progression to invasive cancer associated with Margins involved, Size of the lesion, Age of the patient, Grade of DCIS (if untreated) – 80% high-grade, 40% intermediate-grade, 10% low-grade DCIS lesions become invasive after 10 years.
Paget Disease
- Erythematous eruption with scale crust.
- May be mistaken for eczema.
- Malignant cells arising from DCIS and extending up the lactiferous ducts into the nipple skin without crossing the basement membrane.
- Paget cells can be detected by nipple biopsy or cytologic preparations of the exudate
Lobular Carcinoma In Situ (LCIS)
- Abnormal cells fill lobules (different to those in DCIS)
- Usually incidental, not associated with a mass or micro-classifications
- Can be bilateral and multi-focal
- Associated with increased risk of lobular or ductal carcinoma developing in the same or contralateral breast
- Management: Tamoxifen and close follow-up
- More common in young women
- Dyscohesive cells lacking E-cadherin
Invasive Carcinomas
- Invasive ductal carcinoma (=no special type)-approx. 80%
- Invasive lobular carcinoma approx15%
- Invasive mucinous (colloid) carcinoma 3%
- Invasive medullary carcinoma 3%
- Invasive tubular carcinoma 2%
- Invasive papillary carcinoma 2%
Invasive Ductal Carcinoma
- Presents as a mass detected by physical exam or mammography.
- Advanced tumours may result in dimpling of the skin or retraction of the nipple.
- Macroscopically, hard, irregular border.
- Microscopically, adenocarcinoma, fibrous desmoplastic stroma (scirrhous carcinoma).
Invasive Lobular Carcinoma
- Morphologically distinct variant of breast cancer that occurs in younger women (pre-menopausal).
- Can be bilateral (20%).
- Can be multi-centric within the same breast.
- Cells invade in cords, single file pattern described as “Indian filing".
- Loss of adhesion molecules (E-Cadherin).
- Majority are ER+, HER2-.
Invasive Carcinomas of Special Type
- Invasive tubular carcinoma: Well differentiated, prominent tubules/ducts, Good prognosis (ER+, HER2-)
- Invasive mucinous (colloid) carcinoma: Abundant extracellular pools of mucin, Good prognosis, Seen in elderly women.
- Invasive medullary carcinoma: Circumscribed edge, large malignant cells, surrounding lymphocytic response, Slightly better prognosis than carcinomas of ‘no special type’, Up to 19% of BRCA1 inherited cancers are medullary vs only 2% of sporadic cases.
Inflammatory Breast Cancer
- Any type of breast cancer that has infiltrated the dermal lymphatics
- Red, swollen, and oedematous breast
- Associated with poor prognosis
Mammographic Signs of Malignancy
- Densities
- Calcifications (small, irregular, clustered, linear, or branching)
- Architectural distortion
- Asymmetry
Clinical Symptoms of Breast Cancer
- Breast lump
- Skin dimpling
- Nipple discharge
- Inverted nipple
- Axillary lump
- Skin changes
Spread of Breast Carcinoma
- Local - into surrounding breast tissue, chest wall, and skin ("peau d'orange")
- Lymphatic - axillary, internal mammary, ipsilateral supraclavicular nodes
- Vascular - bone, lung, liver, brain
- Trans-coelomic - pleural cavities
- Recurrences may be local, regional (LN), or distant (systemic)
Staging of Breast Carcinoma (TNM)
- T: Size of primary tumour, involvement of skin and/or chest wall (<2cm, 2-5cm, >5cm, spread to skin or chest wall (fixed or not?))
- N: Regional lymph node status (prognosis related to number involved)
- M: Presence or absence of distant metastases
Histologic Grade
- Scarff Bloom Richardson (3 grades)
- Standardised system to reduce inter-observer variation
- Three features assessed and scored (1, 2, or 3):
- % tubule formation
- Mitotic count
- Nuclear pleomorphism
Prognostic Factors
- Invasive or in situ
- Stage (tumour size, nodal status, evidence of fixation, distant metastases)
- Inflammatory carcinoma
- Histological grade
- Histological subtype of the tumour
- Adequacy of excision
- Lymphovascular invasion
- Proliferative rate
- Angiogenesis
- Gene expression profiling
Predictive Factors
- Expression of hormone receptors (oestrogen and progesterone-80%), Response to anti-oestrogen therapy (e.g. tamoxifen)
- Expression of HER-2, Over-expressed on surface of tumour cells (20-30% of cancers), More aggressive disease, poorer response to systemic treatment, Responds to Herceptin
- Triple negative cancers: Negative for PR, ER, and HER2
Breast Cancer Prognosis
- Overall crude mortality 40% at 5 years, 60% at 10 years.
- 70% if lymph node negative, 30% if lymph node positive.
- Disease more aggressive in younger women.
- Distant metastases: Median survival approximately 12-18 months
Treatment of Breast Cancer
- Surgery (mastectomy or breast conserving)
- Axilla- sentinel node/clearance (sentinel lymph node biopsy - first lymph node draining site)
- Radiotherapy
- Systemic therapy (hormonal, chemotherapy)
- Hormonal (tamoxifen, Arimidex)
- Surgical or chemical ovarian ablation
- Chemotherapy;
- Biological therapy (monoclonal antibodies: Trastuzumab (Herceptin) – inhibition of angiogenesis)
Carcinoma of the Male Breast
- Rare
- Usually occurs in older age groups
- 10% associated with BRCA2 mutations or Klinefelter syndrome (XXY)
- Usually, invasive carcinoma at the time of diagnosis
- Behaves as invasive duct carcinoma of the female breast.
Calcification in Breast Cancer
- Breast cancer cells can produce calcium accumulating and forming small clusters on mammograms(microcalcifications).
- Macrocalcifications are larger calcium deposits not typically associated with breast cancer.
Calcification in Breast Cancer (Mechanism)
- The mechanism(s) producing calcium deposits remains largely unknown, but include aberrant secretion and necrosis.
- Two types of microcalcifications(calcium oxalate and calcium apatite) are distinguished by radiographic "signatures" on mammograms, with calcium apatite correlating more closely with malignant transformation.
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Description
Test your knowledge on the various factors associated with breast cancer, including the role of estrogen metabolites and genetic mutations like BRCA1. This quiz covers risk factors, protective elements, and important syndromes linked to breast carcinoma. Dive into the intricacies of breast cancer and challenge your understanding!
