Breast cancer Flashcards
What is the keynote-522 regimen?
carbo/taxol (TC) + pembrolizumab, followed by doxorubicin/cyclophosphamide (AC)
Adjuvant treatment of DCIS
- None if mastectomy
- ET after BCT is a risk/benefit discussion given no proven OS benefit.
IF ER+ (PR doesn’t matter) AND premenopausal → tamoxifen 20 mg daily for 5 years
IF ER+ and postmenopausal –> AI for 5 years
Class effects of CDK4/6 inhibitors
- Fatigue
- Myelosuppression
- Pneumonitis (2%)
Abemaciclib SE to know
- GI toxicity (nausea, diarrhea)
Schedule of CDK4/6 inhibitors
Abemaciclib is continuous, others are given 3 weeks on 3 weeks off
CDK4/6 inhibitor with good CNS penetration
abemaciclib
CDK4/6 inhibitor with demonstrated OS benefit
ribociclib
Clinical significance of RB1 gene mutation
Confers resistance to CDK4/6
Second line for ER PR + breast cancer patient with PI3k gene mutation
alpelisib + fulvestrant
Second line for ER PR + breast cancer patient with ESR1 gene mutation
elacestrant
Second line for ER PR + breast cancer patient with AKT1 or PTEN
fulvestrant + capivasertib
First line for HER2 positive breast cancer
Trastuzumab + pertuzumab + taxane (THP or DHP)
Second line for HER2 positive
T-Dxd
What is T-Dxd conjugated to?
Topoisomerase I
Third line for HER2 positive
IF no brain mets, T-DM1 (Preferred – Well tolerated. Used to be standard second line) (TH3ERESA – PFS 6.2, OS 22.7)
Given brain mets, tucatinib/capecitabine/trastuzumab (HER2CLIMB - median OS 21.9 months, Preferred if CNS disease because only Phase II data for T-DxD and proven OS benefit)
margetuximab mechanism
HER2 ADC
First line for metastatic TNBC
- Given PD-L1 CPS>10% AND absence of rapidly progressive visceral disease, pembrolizumab for up to 2 years + chemotherapy (taxol vs. abraxane vs. gem/carbo) – (KEYNOTE-355 – mOS 23, mPFS 9.7 months)
- Given PD-L1 negative AND absence of rapidly progressive visceral disease, single agent chemotherapy
***Given extensive and rapidly progressive visceral disease (diffuse, aggressive disease), combination chemotherapy (taxane vs carbo/gem preferred - but no proven OS benefit w/ combination)
Second line for metastatic TNBC
- sacituzumab
- IF HER2 low, T-DxD also an option
Third line for metastatic TNBC
Given BRCA+, olaparib (OlympiAD)
Single agent chemo
IF no neuropathy, Abraxane
Doxil
Gemcitabine
CPS threshold for TNBC first line addition of immunotherapy
10
most common localized breast cancer in terms of receptor phenotype
ER PR +
When it is ok to defer radiation
- Over age 65 + less than 3 cm + node negative + ER positive (can just have adjuvant endocrine)
Other indications for adjuvant radiation to chest wall (if undergoing mastectomy)
*greater than 5 cm
*close margins (less than 1 mm)
- positive lymph nodes
- positive margins
Indications for neoadjuvant systemic therapy in node negative breast cancer
1) Inoperable (Need to shrink tumor to permit BCT or better cosmetic outcome with BCT)
2) Desires BCT but is not a candidate for BCT (Conversion chemotherapy (make operable))
3) Unlikely to have a good cosmetic outcome with BCT (Due to tumor location or size relative to patient’s breast)
Eg. high tumor: breast size ratio
4) Delay in definitive surgery
5) Downstage from limited N1 to N0 (could be candidate for sentinel lymph node biopsy if converted to node-negative with neoadjuvant)
6) Inflammatory breast cancer
7) Select operable breast cancer:
HER2 and TNBC if >cT2
What is ACT
Doxorubicin
Cyclophosphamide
Taxol
Sequencing of chemo vs. radiation adjuvantly for localized breast cancer
Adjuvant chemo is completed before starting XRT (IF no neoadjuvant received) (but institution dependent. decrease risk of radiation recall).
neoadjuvant regimens for TNBC
ACT
TC
CMF
What is CMF
cyclophosphamide
Methotrexate
5-Fu
When you can give TC rather than ACT
small node negative
(low risk (<1cm AND node negative OR cardiac RF’s))
TC?
Taxol
Cyclophosphamide
*but seems also used to refer to taxol carboplatin in breast cancer
Indication for neoadjuvant for TNBC based on size (confirm)
Greater than 0.5 cm
Endocrine therapy for men with breast cancer
tamoxifen
When you can omit adjuvant chemo in ER/PR + breast based on oncotype
- oncotype less than 26 + over the age of 50
- less than 50 (premenopausal)
IF node positive, chemo regardless of score (there was a subset analysis showing benefit but thought to be from ovarian suppression from chemo)
IF node negative, no chemo if <16 (some benefit for intermediate risk)
*just think of as premenopausal only if node negative and <16
Tamoxifen SE’s
- increased risk of endometrial cancer
- increased arterial and VTE risk
- *cataracts
- menopausal symptoms
- weight gain
- hepatic steatosis
*photosensitivity
*bone strengthening but has been shown to cause bone density loss in some women
AI SE’s
- vaginal dryness
- osteoporosis
management of AI induced arthralgias (aside from medication switch)
- duloxetine
- exercise
- acupuncture
Tamoxifen contraindicated with what medication?
- certain SSRI’s - duloxetine or paroxetine
How can you reduce risk of infertility in women after chemo?
GNRH agonists - triptorelin, goserelin
Size cutoff for withholding systemic therapy for HER2
0.5 cm
Size threshold in HER2 disease for which you can use TH (taxol herceptin)
Less than 2 cm
Herceptin contraindication
pregnancy
Management of residual disease after neoadjuvant for HER2+ breast cancer
T-DM1
Management of localized inflammatory breast cancer
Neoadjuvant systemic therapy
Mastectomy w/ axillary nodal dissection
Contraindications in management of breast cancer during pregnancy 1) chemo? 2) endocrine therapy?
- herceptin
- CT scans and nuclear imaging
- chemo can be used in second trimester but ideally postpartum
- XRT
- endocrine therapy
*no axillary nodal dissection since can’t get XRT
locoregional recurrence management in breast cancer
- mastectomy w/ axillary nodal dissection
- radiation if not previously done
- if TNBC adjuvant chemo per CALOR trial (not indicated if HR+)
Genetic syndromes associated with increased risk of breast cancer
BRCA1-2
PALB2
PTEN
ATM
CHEK2
P53
STK11
SDH1
Other
- Thoracic XRT
- ALH/ADH (atypical lobular and atypical ductal hyperplasia)
- Older age
- *early menarchy
- late menopause
When to start screening for breast cancer in patients with history of thoracic breast radiation
30 or 8 years after completion of radiation
Breast cancer screening age now
40
When to start screening BRCA patients
MRI + mammo starting at age 25
*high yield
LCIS management
- surgery +/- endocrine therapy depending on menopausal status (similar to DCIS)
*No XRT
Margin required in DCIS
2 mm
When endocrine therapy is indicated in DCIS
lumpectomy, NOT with mastectomy
Clinical benefit of ET for DCIS
- reduces risk of ipsilateral and contralateral breast cancer recurrence
*no effect on OS
phylodes tumor management + margin size requirement
- surgery alone
*with larger margins (>1 cm)
*hormone therapy is not effective
metastatic phylodes tumor management
taxane based chemo
Contraindications to BCT
- diffuse calcifications
- multifocal disease
- grossly positive margins
*homozygous ATM
Positive lymph node in breast cancer
0.2 mm or greater or >200 cells
Axillary lymph node dissection indications
1) More than 2 positive sentinel lymph nodes on SLNB
2) Clinically palpable axillary lymph node
3) Positive FNA
4) inflammatory breast cancer
5) pregnancy
What is the HER2 climb regimen?
tucatinib/capecitabine/trastuzumab