Oncology 3 - Breast cancer and lung cancer Flashcards
(89 cards)
What are risk factors of breast cancer?
Female gender Increasing age Older age at 1st birth Oestrogen exposure (endogenous/exogenous) EtOH Family Hx
What are genetic features of breast cancer?
20-30% of breast ca pts have affected relative
only 5-10% is gene related
BRCA1, BRCA2, PTEN, p53, ATM, MLH1, MSH2
Some high risk patients have no identifiable gene
What are determinants of high risk breast cancer patients?
Multiple relatives with breast or ovarian ca
Early age of onset
>1 primary Ca (contralateral breast or ovarian Ca)
Vertical transmission (including men)
Rare malignancies in FHx - i.e. sarcomas, breast Ca in Li-Fraumeni syndrome (p53)
Which women with ovarian cancer should undergo BRCA testing?
All women with ovarian cancer, especially those who are
What is the relative contribution of genes to hereditary breast cancer?
BRCA1 - 20-40%
BRCA2 - 10-30%
TP53 -
What are features of BRCA1 and BRCA2 mutations?
DNA repair genes (TSGs)
Autosomal dominant inheritance
Ashkenazi Jews
50-66% lifetime risk of breast cancer
Ovarian cancer 40% BRCA1 risk, 20% BRCA2 risk
Prostate cancer: 40% BRCA2
Pancreatic cancer 5-10% BRCA 1 and 2
Male breast cancer: 2% BRCA1, 5-10% BRCA2
What syndrome is associated with BRCA1?
What is breast ca and ovarian ca risk by 70yo?
What is an associated Cancer?
Hereditary breast/ovarian Ca
Breast cancer risk by 70 50-66%
Ovarian cancer risk 20-40% by 70.
Associated Ca = pancreas
What syndrome is associated with BRCA2?
What is breast ca and ovarian ca risk by 70yo?
What is an associated Cancer?
Hereditary breast/ovarian cancer.
Risk of breast cancer 40-60% by 70.
Risk of ovarian cancer by 70 - 10-20%
Associated Ca = prostate and pancreas
What syndrome is associated with p53?
What is breast ca and ovarian ca risk by 70yo?
What is an associated Cancer?
Li-fraumeni syndrome
>90% risk of BrCa by 70. N/A risk of ovarian Ca.
Associated: soft tissue sarcoma, osteosarcoma, brain tumours, adrenocortical cancer, leukaemia, colon Ca
What syndrome is associated with PTEN?
What is breast ca and ovarian ca risk by 70yo?
What is an associated Cancer?
Cowden syndrome
25-50% risk of breast Ca by 70.
~1% risk of ovarian Ca by 70.
Associated: thyroid, endometrial, GU
What syndrome is associated with STK11/LKB1?
What is breast ca and ovarian ca risk by 70yo?
What is an associated Cancer?
Peutz-Jagher’s sydnrome.
50% risk of breast cancer by 70.
Sex cord tumour risk.
Associated tumours: Small intestine, colorectal, uterine and testicular.
What syndrome is associated with CDH1?
What is breast ca and ovarian ca risk by 70yo?
What is an associated Cancer?
Hereditary diffuse castric cancer
40% risk of lobular breast cancer by 70yo.
N/A ovarian risk.
Associated = diffuse gastric cancer.
What syndrome is associated with MLH1, MSH2, MSH6, PMS1, PMS2?
What is breast ca and ovarian ca risk by 70yo?
What is an associated Cancer?
HNPCC/Lynch syndrome
N/A breast cancer risk
10% risk of ovarian Ca by 70.
Associated: small intestine, colorectal, stomach, uterus, ureter/renal
What are fundamental principles of Mx high risk women?
Consider prophylactic surgery:
- Bilat mastectomy reduces risk by 90%
- BSO reduces risk of breast Ca by 50% (premenopausal), ovarian Ca by 90%
Screening: BSE + q6m clinical breast exam.
Annual mammogram from 40yo (or 5y younger than 1st affected relative)
MRI breast, esp premenopausal.
What role does chemoprevention have in high risk women?
Tamoxifen reduces risk by 40% in pre/post menopausal women.
Raloxifene post menopausal.
OCP reduces ovarian Ca risk, may increase BrCa risk.
What investigations are required when a breast lump is detected clinically?
Triple testing:
- clinical examination
- mammogram +/- USS
- FNA/Core Bx
If palpable lesion is thought to be malignant, should be reviewed by breast surgeon pre Bx
What are poor prognostic features in Breast Cancer? (7)
Positive axillary LNs (MOST IMPORTANT) Increasing size Higher grade (1, 2, 3) Negative hormone receptors (considered positive if ER or PR +ve) Positive HER2/neu (c-erb B2) Younger age Lymphovascular invasion
What are principles of early stage breast cancer management?
Disease confined to breast and axilla.
1) Surgery - WLE/Total mastectomy, sentinel node Bx. Proceed to axillary dissection if sentinel node Bx +ve - straight to axillary dissection if clinically node +ve pre op
2) Adjuvant chemo - 3-6/12
- usually anthracycline and/or taxane based
What are complications of adjuvant chemo?
Hair loss, lethargy, nausea, mucositis
Pancytopenia
Cardiac - anthracyclines, traztuzumab
Anthracyclines (-icin) cause secondary leukaemias in 0.5-1.5%
What is the risk reduction in adjuvant chemotherapy in early stage breast cancer?
40% RR - absolute reduction is related to risk.
Risk of toxicities however are static.
What is an example of a 1st, 2nd and 3rd gen adjuvant regime in early breast ca?
1) Cyclophosphamide, MTX, 5-FU
2) 5-FU, epirubicin, cyclophosphamide
3) dose dense Adriamycin, cyclophosphamide
What advantage does radiotherapy provide in WLE and post-mastectomy?
Provides local recurrence rates similar to mastectomy when used post breast conserving surgery.
Indicated in post mastectomy patients with >5cm breast cancer or >=4 LNs. Recent data shows survival benefit for 1-3 positive LNs.
What is the role of adjuvant endocrine therapy in early breast cancer?
~40% RRR for recurrence
What are examples of SERMs, their MoA, role in early breast cancer and AEs?
tamoxifen, toremifine.
Antagonist on E-receptor in breast or cancer tissue
Agonist on bone, uterus and liver E-receptors
Adjuvant, Used for 5 years, further small red in mort in 10y
Increases BMD in post menopausal women.
risk of VTE, uterine cancer.