Flashcards in Breast Deck (54):
Risk factors for breast cancer?
age at first full term pregnancy (55 years)
hx of atypical breast biopsies
smoking and alcohol consumption
oral contraceptive use (disappears after 10 years of d'c)
For what percentage of heritable breast cancer cases have we identified a mutation?
Common breast cancer syndromes?
BRCA 1 (17q21)
BRCA 2 (Chr 13)
Hereditary diffuse gastric cancer (CDH1)
CHEK2 (Chr 22q)
Criteria for early breast cancer screening?
Have a lifetime risk of breast cancer of about 20% to 25% or greater
- personal or first-degree relative w/ a BRCA1 or BRCA2 gene mutation or heritable condition
- radiation therapy to the chest b/w ages of 10 and 30
Criteria for BRCA 1 / BRCA 2 genetic testing?
-2 or more primary Breast Ca on same side of family
- 1 or more ovarian on same side
- Breast ca in 1st or 2nd degree relative diagnosed before age 45
- Male breast cancer
What is most important prognostic factor for localized breast cancer
# of nodes involved
What are two subtypes of breast adenocarcinoma?
invasive and noninvasive (in situ "basement membrane preserved")
What are two dominant types of invasive breast adenocarcinoma?
ductal (90% of cases) & lobular
What are special subtypes of ductal carcinoma? What special features do they possess?
tubular and mucinous
- usually ER positive with great prognosis
- usually triple negative, commonly seen in BRCA 1 mutation
What is epidemiologic breakdown of ER/PR & HER positive cancers?
ER/PR ~ 70%
HER2 amplification ~ 25%
Triple negative ~ 5% (?10-15%)
What are molecular subtypes of breast cancer?
Luminal A & B (luminal epithelial cells make milk in response to hormones, so usually ER/PR positive; A is low grade, B can be higher grade +/- HER 2)
Basal (myoepithelial cells involved in milk ejection, so usually ER/PR & HER 2 negative)
What is concern for breast DCIS?
Recurrence (as late as 15 years), half are invasive
How is breast DCIS managed? Data?
total mastectomy or lumpectomy + radiation
- Milken trial: at 8 years OS 83.7% vs 85%, DFS 77% vs 80%
For breast DCIS, what is radiation is omitted post-lumpectomy?
increased risk of local recurrence (39% vs 14.3%) - NSABP B-06 trial
How can you guide adjuvant therapy for breast DCIS
Most important factors are: tumor size, tumor grade, presence of necrosis, young age at dx & small margins
- Risk tools that are not validated yet
--Van Nuys Prospective Index (VNPI)
What did NSABP B-17 & EORTC 10853 show regarding adjuvant management of breast DCIS? Limitations of study?
lumpectomy + RT reduced recurrences but did not affect overall survival; 80% of pts had tumor
For patients s/p lumpectomy and RT with extensive DCIS or close margins, what else can one recommend adjuvantly?
Tamoxifen x 5 years for chemoprevention; more effective in ER + cases according to post-hoc analysis
What other breast path findings are consider non-premalignant high risk lesions worthy of chemoprevention with tamoxifen x 5 years?
FEA (flat epithelial atypia)
Breast Cancer Staging Overview
Stage 0: TIS only
Stage I: Tumor 5cm, chest wall, skin or fixed ipsilateral or mammary, infraclavicular or supraclavicular nodes (N2-N3)
Stage IV: metastatic disease
What is pN1mic?
Micrometastasis: >0.2mm but
What metric unit is T stage in and N stage in?
T = cm
N = mm
What is N0(i+)?
Isolated tumor cells:
What grouping is breast cancer therapy divided into?
Early stage: I (maybe adj chemo) -II (def adj chemo)
Locally Advanced: III (neoadj chemo)
Metastatic: IV (chemo only)
What is initial treatment recommendation for Stage I Breast hormone positive cancer? What if she is > 70 years of age?
-Total Mastectomy or Lumpectomy with sentinal lymph node biopsy & radiation (NSABP B-06)
- Lumpectomy alone (CALBG 9343) - local recurrence are higher but OS similar
What should be done for positive SLN biopsy in Stage I hormone positive breast cancer? Data?
If pN1mic (
What is common adverse consequence of ALND?
What is adjuvant therapy for Stage I node-negative hormone positive breast cancer? How can one decide?
consider chemotherapy based on risk of recurrence followed by hormone therapy
- can use Oncotype Dx
What are risk groups for Oncotype Dx? Likely treatment recs?
Low (score 31): chemo + hormone therapy
What is adjuvant chemotherapeutic regimen for Stage I Breast cancer?
AC-T (anthracycline, cyclophosphamide and taxane) or TC (better than AC alone US Oncology Research trial 9735)
What are your two main initial options for adjuvant hormone therapy in breast cancer? Which preferred in which setting?
tamoxifen (pre-menopausal) & aromatase inhibitors (post-menopausal)
What are side effect profiles for tamoxifen versus AIs?
Tamoxifen = venous thrombosis & endometerial cancer (absolute increase of 0.5% at 10 years)
AIs: arthralgias & osteoporosis
What is recommended duration of hormone therapy?
Tamoxifen 10 years
AI for at least 2, up to 5
patients on tamoxifen can be switched to AI if postmenopausal (2-5 years of tamox + 5 AI)
What classifies post-menopausal?
Amenorrhea for 12 months (24 months if chemo-induced) with a consistent hormone profile
Clinicopathologic factors that influence risk of recurrence?
# of positive nodes (most important* if positive, go chemo)
What is treatment recommendation for early stage TNBC?
-standard is surgery +/- RT followed by AC-T
-phase II neoadjuvant studies are promising, particularly with platinum agents; PARP also; but not standard neoadjuvant recs for early stage
What is risk reduction strategy for BRCA 1 carriers?
b/l mastectomy and b/l oophorectomy
What is testing protocol and criteria for HER2 in breast cancer?
IHC: 3+ is positive; if 2
-single probe requires copy # of > 6 signal/cell
What clinical diagnosis should one consider for a breast cancer patient with inflammatory changes over breast that began
Inflammatory breast cancer
- mortality is 20-50% at 5 years
How is stage III breast cancer best managed? What is the likelihood of tumor progression during this time?
1-2% (therefore operability is not affected)
What outcome with neoadjuvant therapy predicts for improved DFS and OS?
What is neoadjuvant recommendation for HER2+ tumors? Data?
pertuzumab + trastuzumab + docetaxel for 4 cycles
- Neosphere trial, combination arm pCR 45%, doce + trast pCR 29% and mono anti HER2 was ~ 16.8%
What is adjuvant recommendation for HER2+ tumors? What is concern with this strategy? Data?
trastuzumab for 9-12 mos; cardiac disease
-NSABP B-31, AC-T +/- trast, NEJM 2005: 12% |difference| in DFS and 33% |reduction| in death at 3 years
What % of invasive breast carcinoma develop mets? When? What is approx median OS?
20-30% in first 5-10 years
-median OS 2 years, varies by tumor subtype
Common sites of mets for IDC and ILC?
IDC= lungs, pleura, brain
ILC= bone marrow, peritoneum
What is preffered management for metastatic breast cancer?
hormone therapy; agent of choice
premenopausal= tamoxifen with hormone ablation
postmenopausal= aromatase inhibitor
What can be seen with tamoxifen that predicts excellent response?
tumor flare; generally self-resolve in a few weeks but can be given steroids
What do aromatase inhibitors work better in post menopasual setting?
principal source of estrogen derived from peripheral conversion of adrenal hormones (ovaries are shutdown)
What agent is now added with hormone therapy for improved PFS? Data?
- BOLERO-2 trial: hormone+ MBC with relapse on AI given exemestane +/- everolimus; median PFS 10.6 vs 4.1 months
Preclinical studies show this agent is effective in resistent ER+ breast cancer? Data?
CDK -4/6 inhibitor
Phase II showed PFS of 20 vs 10 months in Palbociclib +/- letrozole
What is treatment recommendation for hormone-resistant metastatic breast cancer? If HER2+?
single agent chemo (combo vs single does not improve OS but increase toxicity)
- capecitabine, gemcitabine
* if HER+
- (previously treated) lapatinib + trastuzumb
- (untreated 1st line) pertuzumab, trastuzumab, docetaxel (CLEOPATRA trial)
- (2nd line)TDM-1 (trastuzumab emtansine
What is given every 4 weeks for breast cancer patients with bone mets?
zolendronic acid (better than pamidronate, SE include osteonecrosis of jaw, renal insufficency and ocular inflammation)
denosumab (best, human RANKL antibody, increased rate of hypocalcemia)
What are the two types of AI's?
nonsteridal: anastrozole, letrozole
What can safely be given to pregant patients with breast cancer during 2nd & 3rd trimesters?
Anthracyclines, cyclophosphamide & 5-Fu