Breast cancer Flashcards
Indication for obtaining oncotype score
Assesses 16 cancer-related genes and 5 normal comparator reference genes, and is therefore sometimes known as the 21-gene assay.
**It was designed for use in estrogen receptor (ER) positive tumors. The test is run on formalin fixed, paraffin-embedded tissue. Oncotype results are reported as a Recurrence Score (RS), where a higher RS is associated with a worse prognosis, referring to the likelihood of recurrence without treatment. In addition to that prognostic role, a higher RS is also associated with a higher probability of response to chemotherapy, which is termed a positive predictive factor.
interpretation of oncotype score
For women older than 50 years of age:
Recurrence Score of 0-25: The cancer has a low risk of recurrence. The benefits of chemotherapy likely will not outweigh the risks of side effects.
Recurrence Score of 26-100: The cancer has a high risk of recurrence. The benefits of chemotherapy are likely to be greater than the risks of side effects.
For women age 50 and younger:
Recurrence Score of 0-15: The cancer has a low risk of recurrence. The benefits of chemotherapy likely will not outweigh the risks of side effects.
Recurrence Score of 16-20: The cancer has a low to medium risk of recurrence. The benefits of chemotherapy likely will not outweigh the risks of side effects.
Recurrence Score of 21-25: The cancer has a medium risk of recurrence. The benefits of chemotherapy are likely to be great than the risks of side effects.
Recurrence Score of 26-100: The cancer has a high risk of recurrence. The benefits of chemotherapy are likely to be greater than the risks of side effects.
anthracyclines
*All the -rubicins
Doxorubicin, epirubicin, idarubicin, daunorubicin, Pegylated liposomal doxorubicin
Perjeta generic name
pertuzumab
high risk features of early stage breast cancer
high-grade tumor, large tumor size (≥2 cm), pathologically involved lymph nodes, and/or high 21-gene recurrence score
what is atypical ductal hyperplasia (ADH)?
Precursor to DCIS
duration of adjuvant endocrine therapy
Given node+ (>3), continue ET for 10 years (ATLAS – DFS + OS benefit)
Given 1-3 (CONFIRM), Determine Breast cancer index (BCI) to predict risk
Given node negative (<3)
high risk of recurrence (based on breast cancer index) → continue ET for 10 years (ATLAS)
low risk of recurrence → continuation for 5 years is individualized
Highest risk race for breast cancer
Higher risk among white females
Histologic subtypes of in situ breast cancer
Ductal
Lobular
most favorable histologic subtypes
Tubular and mucinous
Define the histologic subtypes of breast cancer
- Invasive ductal carcinoma
- lobular
- mixed
- mucinous
- tubular
- medullary
- metaplastic
- papillary
- cribriform
most common histologic subtypes
infiltrating ductal (75%) infiltrating lobular (5-10%)
Receptor phenotype of lobular carcinoma
- vast majority are ER positive + display loss of E-cadherin
Role for clinician and self breast exams
Some organizations recommend clinical breast exam yearly after age 40. Breast SELF-exam not recommended.
- mammogram features concerning for malignancy
- feature suggesting benignity
- spiculated soft tissue mass (most specific)
- microcalcifications
- irregularly outlined more common than rounded
- solid mass suggests benign
Clinical utility of US
- distinguishing between cystic and solid masses
- further information on likely of a solid mass being malignant
Test characteristics + clinical utility of MRI for assessment of breast cancer
Most sensitive modality but low specificity (benign breast lesions also enhance), but improvement in specificity hasn’t shown survival benefit in preoperative planning
- Complement to mammogram for dense breasts
- for invasive cancers contiguous to the chest wall, MRI may be needed for surgical planning.
effect of ER and PR status on breast cancer prognosis
ER/PR-negative tumors have a worse prognosis
what is oncotype DX?
- 21-gene assay that provides a numerical score to quantify risk of recurrence for ER positive breast cancer
- also predictive of adjuvant chemotherapy benefit
Management of lobular carcinoma in situ (LCIS)
Primary surgery, followed by risk reduction – (tamoxifen, raloxifine, aromatase inhibitors, bilateral prophylactic mastectomy)
Risk of future invasive breast cancer in a patient with LCIS?
1% per year
Management of DCIS
Mastectomy with SLNB OR lumpectomy with XRT
- tamoxifen if ER positive, unless undergoing bilateral mastectomy
Survival benefit of mastectomy versus lumpectomy
None
Initial treatment options for operable, early stage breast cancer?
1) Lumpectomy with surgical staging of the axillary lymph nodes
2) Total mastectomy with surgical staging of the lymph nodes
3) Neoadjuvant chemotherapy to permit breast conserving therapy
Next step for BiRads 0
Additional evaluation is required for further characterization, which may include additional mammographic views and or ultrasound and, rarely, magnetic resonance imaging (MRI).
why microcalcifications suggest breast cancer
They are intraductal calcifications in areas of necrotic tumor
management of brca 1 and 2 carrier and age
BRCA1 carrier:
Bilateral salpingo-oophorectomy by age 35-40 after childbearing (earlier in BRCA1)
+ Prophylactic bilateral mastectomies
BRCA2 carrier:
Bilateral salpingo-oophorectomy by age 40-45
Prophylactic bilateral mastectomies
what is the function of aromatase?
converts circulating androgens to estrogen
Name some of the common non-trastuzumab-based regimens for neoadjuvant and adjuvant treatment of breast cancer
ACT (docetaxel, doxorubicin, cyclophosphamide) (taxane-AC)
Dose-dense AC
TC (docetaxel/cyclophosphamide)
what is is AC regimen?
doxorubicin/cyclophosphamide
Firstline systemic therapy for HER2-positive metastatic disease
trastuzumab + pertuzumab + taxane until maximum tumor response, followed by maintenance trastuzumab + pertuzumab
Palbociclib indication
ER/PR+ metastatic breast cancer in postmenopausal women
indication for lapatinib
Second line for HER2-positive breast cancer (confirm)
Management of fibroadenoma
- Primary surgery
- path to rule out phyllodes tumor
What is a phyllodes tumor
Large, fast-growing masses that form from the periductal stromal cells of the breast.
Upper limit of breast cancer screening per ASCO and underling point
Life expectancy of 10 or more years. It should really be individualized based on someone’s health status, not some arbitrary cutoff.
Stage at which most patients present
Vast majority present without metastatic disease
Locally advanced includes which stages?
IIIA-IIIC
Subset of patients with IIb
Early stage breast cancer includes
Stage I, IIA, or subset of IIb
Management of early stage breast cancer
Primary surgery and surgical axillary staging with or without RT
Adjuvant chemo depending on tumor size, grade, number of involved lymph nodes, ER/PR status, HER2
However — triple negative typically treated with neoadjuvant chemo
Criteria precluding BCT
Multi centric disease
Large tumor size in relation to breast
*Diffuse malignant calcification on imaging
*Prior chest RT
Persistently positive margins despite attempts at re-excision
Initial workup (in addition to imaging)
1) Bilateral mammogram
2) US
3) Determination of ER/PR status and HER2
4) Genetic counseling if at risk for hereditary breast cancer syndrome
5) Pregnancy counseling
6) Imaging based on symptoms
PET/CT if stage IIIA or higher
Management of early stage patient with suspicious axillary lymph nodes
US + FNA or core biopsy
Management of patient with early stage BC and positive biopsy of axillary nodes
If going directly to surgery — axillary node dissection
Management of patient with early stage BC and negative biopsy of axillary nodes
Sentinel lymph node biopsy at time of surgery
Management of early stage patient with negative axillary examination
SLNB at time of surgery
Role for HER2-directed therapy in early stage
Used if tumor is greater than 1 cm, in combination with chemo.
Use for small cancers is controversial.
Adjuvant management of triple negative early stage breast cancer AND indication
Adjuvant chemo if tumor greater than 0.5 cm
Goal of systemic therapy for locally advanced BC
Induce a tumor response and enable BCT
Management of patient progressing on neoadjuvant systemic therapy
Proceed directly to surgery rather than switching regimen
Management of patient who has complete clinical and/or radiographic response to NAC
Proceed to surgery still
Role for adjuvant therapy in locally advanced
— HER2 positive following completion of surgery to complete a year of treatment
— continue endocrine therapy
Breast cancer surveillance
Annual diagnostic mammo for 3-5 years then switch to screening mammo
Prognostic significance of intramammary lymph nodes
Worse prognosis
Mammogram laterality in surveillance
IF mastectomy –> no need
IF BCT –> still need
Always need bilateral otherwise (women with BC in one breast are at higher risk of breast cancer in other breast)
Risk factors for breast cancer
- Age
- White
- Dense breast tissue
- Obesity
- Hormone therapy
- Smoking (modest)
- RT (hodgkins patients)
- Increased age at first full-term pregnancy
Role for clinical breast exam
As part of physical exam in surveillance period
Options for risk reduction following surgery for LCIS
tamoxifen, raloxifine, aromatase inhibitors, bilateral prophylactic mastectomy
adriamycin generic name
doxorubicin
Palbociclib mechanism
CDK4/6 inhibitor
lapatinib mechanism
Small molecule inhibitor of VEGF + HER2
Generally what differentiates early stage from locally advanced
presence of axillary adenopathy
Common mechanism of resistance to anti-estrogen therapy
activation of the mTOR signaling pathway
Phenotype of most BRCA1 breast cancers
triple negative
Phenotype of most BRCA2 breast cancers
ER+
Additional cancer types associated with BRCA2
- ovarian, gastric, melanoma, prostate, pancreatic
Additional cancer types associated with BRCA1
- ovarian
SRE reduction in anyone on an aromatase inhibitor
Zometa for up to 2 years
When to start screening women for breast cancer who’ve had chest wall radiation (eg for hodgkins)
- 10 years after XRT OR at age 40, whichever comes first
Management of localized tubular carcinoma of the breast
Partial mastectomy with axillary sentinel lymph node biopsy
tubular carcinoma of the breast clinical behavior
Excellent outcomes, do well
First line for postmenopausal woman with ER, PR + breast cancer
CDK4,6 inhibitor + AI (letrozole)
First line neoadjuvant for locally advanced triple negative breast cancer?
carbo/taxol + pembrolizumab, followed by doxorubicin/cyclophosphamide
Management of residual disease after neoadjuvant therapy in locally advanced breast cancer
Capecitabine
adjuvant therapy in early stage for HER2+, ER+
taxol-trastuzumab followed by aromatase inhibitor
Firstline for triple negative MBC
Chemoimmunotherapy
Pembro if CPS greater than 10
First line for triple negative MBC + chemo options
Single agent chemo(taxol vs. abraxane vs. gem/carbo) +- IO if PD-L1 CPS greater than 10%
First line for HER2 positive MBC
Trastuzumab + pertuzumab + taxane
Imaging modality + frequency needed for hodgkin’s patients treated with chest wall radiation
annual mammogram + MRI
Second line for HER2 + metastatic
Trastuzumab deruxtecan (T-DXd) (newer ADC w/ higher payload + bystander effect) (DESTINY-Breast03)
Adjuvant therapy for male breast cancer
Tamoxifen (can’t use AI due to concerns it may lead to incomplete estradiol suppression)
What is TCHP?
Docetaxel (Taxotere)
Carboplatin (Paraplatin) Trastuzumab (Herceptin) Pertuzumab (Perjeta)
Indications for neoadjuvant chemotherapy with HER2+ disease
Node positive or large tumors (greater than 2 cm)
Management of HER2 positive breast cancer with pathCR
continue trastuzumab with pertuzumab (Dual HER2 blockade) for total 1 year
Management of HER2 positive with incomplete response to NAC
adjuvant ado-trastuzumab emtansine (T-DM1) for 14 cycles, rather than trastuzumab (KATHERINE)
when raloxifene is indicated
postmenopausal
Indications for neoadjuvant for triple negative
T2 or T1N+ (CONFIRM)
Additional RF
OCP’s (patients at increased risk, with family members with BC) should consider stopping oral contraceptives
Intervention with survival benefit in BRCA patients
BSO
bilateral mastectomy has NOT been shown to have a survival benefit
Drug indicated for PIK3CA + for what receptor status
- alpelisib
- hormone receptor positive
Role for PIKC3A therapy in breast
Second line for metastatic hormone receptor positive
Indication for bisphosphonate in breast cancer
IF adjuvant therapy planned AND postmenopausal REGARDLESS of receptor phenotype
Sequencing of adjuvant XRT, endocrine, and chemotherapy for adjuvant hormone positive
Adjuvant chemotherapy, radiation therapy, followed by adjuvant endocrine therapy
Nodal involvement warranting adjuvant radiation therapy
More than 3
T-Dxd payload mechanism of action
Topoisomerase inhibitor
NAC for HER2 positive and why
Trastuzumab/pertuzumab + nonanthracycline based chemo (TCHP)
- study showed nonanthracyclne based regimen had similar OS, so TCHP is less toxic with comparable outcomes
what is considered locally advanced disease
*T3 or greater, N2 or N3 disease
Adjuvant therapy for early stage node negative HER2+ breast cancer
Taxol + trastuzumab (de-escalation appropriate)
Management of breast cancer in patient with Li fraumeni syndrome
mastectomy rather than lumpectomy with radiation (high risk of recurrent cancer so no radiation)
BiRADS 2 management
Repeat mammogram every 6-12 months for 2-3 years to document stability
IF enlarging, biopsy
BI-RADS 2 management
Continue regular screening
Evidence for PARP inhibitors for BRCA mutant patients with metastatic disease
PFS but no OS benefit so not recommended (Confirm)
Risk of developing contralateral breast cancer in BRCA2 mutant patient with breast cancer over 20 years AND risk of developing ovarian cancer
25%
- ovarian cancer - 15-20%
Which BRCA mutation is higher risk for ovarian cancer? What is the risk over 20 years?
BRCA1 (40-45%)
NAC regimen for PD-L1 positive triple negative
carbo/taxol + pembrolizumab, followed by doxorubicin/cyclophosphamide
Adjuvant endocrine therapy in premenopausal woman
ovarian suppression + aromatase inhibitor
Surveillance modality for patients who’ve had chest wall radiation
annual breast MRI (after age 25 years) and annual screening mammogram (after age 30 years). MRI and mammogram are often alternated every six months.
Systemic therapies contraindicated in pregnancy
- HER2-directed therapy
- antiestrogen therapy
*you can use anthracyclines and cytoxan during second trimester
When is axillary lymph node dissection required after surgery in breast?
Greater than 3 lymph nodes involved on sentinel lymph node biopsy
