Lecture 9.2: Breast Disease Flashcards
Symptoms of Breast Disease
Pain
Lump in Breast
Skin Changes (Excoriation)
Nipple Disorders
What is Fibrocystic Breast (Fibroadenosis)?
- Breast tissue becomes composed of tissue that feels
lumpy or rope like in texture - This called nodular or glandular breast tissue
- Occurs mostly between 30 and 50
- Linked to Oestrogen
What is Benign Mammary Dysplasia?
A group of conditions marked by changes in breast tissue that are benign
Chronic Mastitis
- Occurs in women who are not breastfeeding
- In postmenopausal women, breast infections may be
associated with chronic inflammation of the ducts
below the nipple
Inflammatory Conditions of the Breast (3)
- Acute Mastitis
- Mammary Duct Ectasia
- Fat Necrosis
What is Acute Mastitis/Lactation (Puerperal Mastitis)?
- Usually a bacterial infection and is seen most
commonly in the postpartum period - Bacteria invade the breast through the small erosions
in the nipple of a lactating woman, and an abscess can
result
What is Mammary Duct Ectasia?
A benign breast condition that occurs when a milk duct in the breast widens and its walls thicken
What is Fat Necrosis?
Fat tissue in the breast or other organs is damaged by injury, surgery, or radiation therapy
What is Gynaecomastia?
A common condition that causes boys’ and men’s breasts to swell and become larger than normal
Name 3 Benign Tumour-Like Lesions
- Fibroadenoma
- Intraduct Papilloma
- Lipoma
Examples of Malignant Neoplasms (4)
- Ductal Adenocarcinoma
- Lobular Adenocarcinoma
- Sarcoma
- Metastasis from other tissues
What can cause Mastitis? (4)
- Infection
- Congested Milk
- No Hygiene
- Baby sucks wrong
What are Intraductal Papillomas?
They are benign (noncancerous), wart-like tumours that grow within the milk ducts of the breast
What is Sclerosing Adenosis?
It is a benign proliferative condition of the terminal
duct lobular units characterised by an increased number of acini and their glands
What are Fibroadenomas?
Benign breast tumours consisting of both glandular and connective tissue: most common in women in their 20s and 30s
What percentage of patients survive breast cancer for 10 or more years after the diagnosis?
76%
Most breast cancers are ……, which are tumours that start in the epithelial cells that line organs and tissues
carcinomas
Types of Breast Carcinomas and their Percentage Prevalence? (3)
- Invasive ductal carcinoma (50-70%)
- Ductal carcinoma in situ (20%)
- Invasive lobar carcinoma (10%)
Pre-Invasive Breast Cancer: DCIS
- Ductal Carcinoma in situ
- Spreads through ducts and distorts ductal architecture
- Can progress to invasive cancer
- Unilateral
Pre-Invasive Breast Cancer: LICS
- Lobular Carcinoma in situ
- Does not distort ductal architecture
- Bilateral
- Risk factor not a precursor
Invasive Breast Cancer: NST
- Ductal Carcinoma No Special Type
- Develops from DCIS
- Fibrous response to produce a mass
- Metastasises via lymphatics and blood
Invasive Breast Cancer: ILC
- Lobular Carcinoma
- Isolated Tumour Cells (CDH1 mutations)
- Minimal Fibrous Response
- Metastasises preferentially via viscera
1 in XYZ women in the UK will develop breast cancer during their lifetime. What is the number XYZ?
7
Risk Factors Breast Cancer, Name 5 (15)
- Increased Age
- Early Menarche (before 11)
- Having the first pregnancy after age 30
- Not breastfeeding
- Never having a full-term pregnancy
- Late menopause (after 55)
- Endogenous Hormones
- Oral Contraceptives
- Hormone Replacement Therapy (HRT)
- Breast Density
- Family History
- Ionising Radiation
- Overweight and Obesity
- Alcohol
- Smoking
Breast Cancer Symptoms (9)
- Lumps
- Nipple Discharge
- Dimpling
- Breast or Nipple Pain
- Nipple Retraction/Inversion
- Redness
- Changes in Skin Texture
- Lymph Node Changes
- Swelling (changes in shape/size)
How is Breast Cancer diagnosed? (6)
- Screening
- Mammography
- Ultrasonography
- MRI
- Biopsy
- Histopathological Analysis
What Biomarkers confirm Breast Cancer Diagnosis
- Ki67
- Oestrogen Receptor
- Progesterone Receptor
- HER2
Stage 1 Breast Cancer
- Tumour is no more than 2cm in diameter
- Cancer hasn’t spread to lymph nodes
- Cancer hasn’t spread outside of breast
Stage 2 Breast Cancer
- Tumour is 2-5cm in diameter & cancer may have
spread to axillary lymph nodes - Tumour is 5cm in diameter but not spread to axillary
lymph nodes - Tumour is less than 2cm in diameter but cancer has
spread to more than 3 axillary lymph nodes
Stage 3 Breast Cancer
- Tumour is more than 5cm in diameter & cancer cells
have spread to axillary lymph nodes, however nodes
are unconnected - Tumour is smaller than 5cm in diameter & cancer cells
have spread to nearby lymph nodes & nodes are
growing into each other - Tumour is smaller than 5cm in diameter but cancer
has spread to lymph node above collarbone
Stage 4 Breast Cancer
Metastatic Breast Cancer
Common Metastatic Sites in Breast Cancer
- Axillary Lymph Nodes
- Mammary Internal Chain Lymph Nodes
- Lungs
- Bones
- Liver
- Peritoneal Metastasis
Breast Cancer Molecular Subtypes (5)
- Luminal A
- Normal-Like
- Luminal B
- HER2-enriched
- Triple Negative
What is the Oncotype DX Test?
- It is a genomic test used for early stage, ER+, HER2-
breast cancers that analyses the expression of 16
cancer-related genes - These can affect how an early-stage breast cancer is
likely to behave and respond to treatment
How is the Oncotype DX Test a prognostic test?
Provides more information about how likely (or unlikely) the breast cancer is to come back
How is the Oncotype DX Test a predictive test?
Since it predicts the likelihood of benefit from chemotherapy or radiation therapy
Breast Cancer Management
Slide 33 & 34
Breast Cancer Treatments (5)
- Surgery
- Hormones
- Targeted Therapy
- Radiotherapy
- Chemotherapy
Adjuvant & Neoadjuvant Chemotherapy Drugs (5)
- Anthracyclines (doxorubicin)
- Taxanes (paclitaxel)
- 5-fluorouracil (5-FU)
- Cyclophosphamide
- Carboplatin
What strategies are used to treat hormone-sensitive breast cancer? (4)
- Ovarian ablation by surgery (oophorectomy) or by
radiation - Treatment with gonadotropin-releasing hormone
(GnRH) agonists, aka luteinizing hormone-releasing
hormone (LHRH) agonists (goserelin and leuprolide) - Blocking oestrogen production via Aromatase
Inhibitors - Blocking oestrogen’s effects via selective oestrogen
receptor modulators (SERMs) such as tamoxifen
Examples of Aromatase Inhibitors
- Anastrozole
- Letrozole
- Exemestane
Aromatase Inhibitors MOA
Lower oestrogen levels by stopping an enzyme in fat tissue (called aromatase) from changing other hormones into oestrogen
How does Oestrogen cause cancer?
Cells from these types of cancer have receptor sites that bind to oestrogen, which promotes their growth and spread
Tamoxifen MOA (Hormone Therapy)
Tamoxifen is metabolised via CYP2D6 into endoxifen, its primary active metabolite that blocks ER,
Are Aromatase inhibitors or Tamoxifen better at reducing risk of breast cancer recurrence in premenopausal and postmenopausal women?
Aromatase inhibitors
Targeted Therapy: Trastuzumab/Herceptin MOA (3 MOAs)
It is a humanised monoclonal antibody against HER2 receptor
1) Binding to HER2 results in inhibition of downstream
pathways including MAPK and PI3K/Akt that lead to
proliferation
2) Binding to HER2 attracts immune cells to tumour site
and promotes ADCC
3) Binding to HER2 results in receptor internalisation
and degradation
Targeted Therapy: Pembrolizumab MOA
- A checkpoint inhibitor that targets the PD-1/PD-L1
pathway - Has been approved in combination with
chemotherapy for patients with metastatic, PD-L1-
positive triple-negative breast cancer (TNBC)
What percentage of Breast Cancers are Familial Breast Cancer?
5-10% (vast majority of cancers are sporadic)
What causes Familial Breast Cancer?
Characterised by mutations in BRCA1 and BRCA2
tumour suppressor genes that lead to loss of function of BRCA1 and BRCA2 proteins
The lifetime risk of developing breast cancer in
women inheriting a BRCA1 mutation is …%?
55-65%
The lifetime risk of developing breast cancer in
women inheriting a BRCA2 mutation is …%?
45%
What other cancers are linked to BRCA1 and BRCA2 mutations?
- Ovarian Cancers
- Prostate Cancers
Potential for Cancer Biomarkers (6)
- Estimate Risk of Developing Cancer
- Screening
- Differential Diagnosis
- Determine Prognosis of Disease
- Predict Response to Therapy
- Monitor for Disease Recurrence
BRCA1 and BRCA2 proteins are Caretakers of
Chromosomal Stability, what does this mean?
They promote high fidelity homologous recombination repair of double-stranded DNA (DSDNA) breaks
Targeted Therapy for Familial Breast Cancer
- PARP (poly(ADP-ribose) polymerase) inhibitors are
used for the treatment of germline BRCA-mutated,
HER2-negative breast cancers - The most widely used PARP inhibitor is currently
olaparib (Lynparza) - PARP plays a central role in DNA repair including DNA
damage caused by alkylating agents & chemo-
therapeutic drugs
What is the NHS Breast Screening Programme?
- Invites all women from the age of 50 to 70 for
screening every 3 years - Breast screening uses a test called mammography
which involves taking x-rays of the breasts
Breast Cancer Self Examination
Monthly breast self-exams can help to detect changes that may be signs of infection or breast cancer (such as breast lumps or spots that feel different)
Breast Cancer Prevention (3)
- Increased Mammography
- Elective Surgery
- Chemoprevention
