Metastatic/Recurrent Breast Cancer Flashcards
METASTATIC BREAST CANCER TREATMENT
Goals of therapy
Goals of therapy: palliation, prolongation of life (if possible) and to maximize quality of life; cure is
not likely (< 5% at 10 years); however, in some selected patients, disease may be controlled for many
years with good QOL.
METASTATIC BREAST CANCER TREATMENT
Response based on type
- Bone and Soft Tissue Mets: tend to have better prognosis and more likely to respond to endocrine
- Systemic visceral metastases generally require chemotherapy due to need for rapid response
- Brain mets: generally do not respond to chemo
HR receptor positive breast cancers tend to be more indolent and respond better to endocrine vs. HR-negative
- ER/PR or HER2 status can change w/ treatment and progression
METASTATIC BREAST CANCER TREATMENT
Olaparib
Biomarker
BRCA1/2 mutations
(germline sequencing)
Line of therapy:
ANY
METASTATIC BREAST CANCER TREATMENT
Talazoparib
Biomarker
BRCA1/2 mutations
(germline sequencing)
Line of therapy:
ANY
METASTATIC BREAST CANCER TREATMENT
Larotrectinib
Biomarker
NTRK fusion
Subsequent (after no
other satisfactory
alternative
treatments)
METASTATIC BREAST CANCER TREATMENT
Entrectinib
Biomarker
Subsequent (after no
other satisfactory
alternative
treatments)
METASTATIC BREAST CANCER TREATMENT
Pembrolizumab
Biomarker
MSI-H/dMMR
Tumor Mutational Burden High (TMB-H) defined as ≥
10 muts/mb
TNBC - PD-L1 expression
METASTATIC BREAST CANCER TREATMENT
Dostarlimab-gxly
Biomarker
Tumor Mutational BurdenHigh (TMB-H) defined as ≥
10 muts/mb
METASTATIC BREAST CANCER TREATMENT
Alpelisb + fulvestrant
Biomarker
Breast Cancer Subtype: HR-positive/HER2-negative
PIK3CA activating mutation
METASTATIC BREAST CANCER TREATMENT
Pembrolizumab +
chemotherapy (albumin bound paclitaxel,
paclitaxel, or gemcitabine +
carboplatin)
Biomarker
Breast Cancer Subtype: TNBC
PD-L1 expression using
22C3 antibody (threshold for positivity combined positive score (CPS) ≥ 10)
METASTATIC BREAST CANCER TREATMENT
Endocrine Therapy
TARGETS
1) inhibit or eliminate production of estrogen:
- Oophorectomy or LHRH agonist (PREmenopausal)
- Aromatase Inihibitor (POSTmenopausal)
2) Block effect of estrogen at cellular level:
- Selective estrogen receptor modulators (SERMs) - PRE/POSTmenopausal
- Selective estrogen down regulators (SERDs) - POSTmenopausal
METASTATIC BREAST CANCER TREATMENT
Endocrine Therapy
SERMS (pre and post menopausal)
PRE/POSTmenopausal
- Tamoxifen
- Toremifene: no advantage over tamoxifen, less data
Near complete cross resistance between SERMs
METASTATIC BREAST CANCER TREATMENT
Endocrine Therapy
AI
- anastrazole
- letrozole
- exemestane
METASTATIC BREAST CANCER TREATMENT
Endocrine Therapy
Selective Estrogen Receptor Down-regulators (SERDs)
Fulvestrant
- Approved for use in HR-positive, HER2-negative advanced breast cancer in postmenopausal women w/ disease progression following endocrine tx
METASTATIC BREAST CANCER TREATMENT
Endocrine Therapy
LHRH agonists
- Leuprolide - not approved in US for breast cancer. Use in premenopausal pts only
- Goserelin - similar efficacy to leuprolide. Approved for advanced breast CA in US
- Triptorelin - Phase 2 trials indicate significant response in HR-positive pts as first line tx for metastatic BRCA
METASTATIC BREAST CANCER TREATMENT
Endocrine Therapy
Sequencing
Sequential HT should be offered to patients with endocrine-responsive dx
No specific order of agents recommended
If patient responds to tx, predicts benefit to another agent
NCCN guidelines recommend chemo for patients with no clinical benefit after up to 3 sequential endocrine tx regimens
METASTATIC BREAST CANCER TREATMENT
Endocrine Therapy
Combination vs. Sequential Single Agents
Sequential hormone therapy is preferred for most women with HR-positive MBC except in cases
of immediately life-threatening disease or those with rapid visceral recurrence during adjuvant
endocrine therapy
First line treatment with fulvestrant plus a non-steroidal AI may be offered as first-line
treatment
METASTATIC BREAST CANCER TREATMENT
Endocrine Therapy
Premenopausal women
ASCO guidelines strongly recommend OAS in combination with treatment options as recommended for postmenopausal women
- tamoxifen or OAS alone (new pts)
Premenopausal women who develop metastatic disease while receiving adjuvant tamoxifen or within 12 months of treatment should be treated with OAS + AI.
METASTATIC BREAST CANCER TREATMENT
Endocrine Therapy
NCCN Guidelines
HER2-Negative and Postmenopausal or
Premenopausal Receiving OAS
Preferred Regimens: 1st line
- CDK4/6 inhibitor + AI
- CDK4/6 inhibitor + fulvestrant
- SERD (fulvestrant) +/- non steroidal AI (anastrozole, letrozole)
METASTATIC BREAST CANCER TREATMENT
Endocrine Therapy
NCCN Guidelines
HER2-Positive and Postmenopausal or
Premenopausal Receiving OAS
- AI +/- trastuzumab
- AI +/- lapatinib
- AI +/- lapatinib + trastuzumab
- Fulvestrant +/- trastuzumab
- Tamoxifen +/- trastuzumab
METASTATIC BREAST CANCER TREATMENT
Chemotherapy
When to consider Chemo Tx
Consider first-line chemotherapy for patients with:
a. ER/PR negative tumors
b. Symptomatic, visceral sites of metastases (visceral crises)
c. Faster growing; high ki-67
METASTATIC BREAST CANCER TREATMENT
Chemotherapy
Combination vs. sequential single agents
Sequential single agents are preferred, but chemotherapy combinations may be used in select
patients with high tumor burden, rapidly progressing disease, and visceral crisis
Combination regimens are generally associated with higher response rates compared to single agent chemo
METASTATIC BREAST CANCER TREATMENT
Chemotherapy
Combination vs. sequential single agents
A → T vs T → A vs AT (A = doxorubicin, T = paclitaxel).
Response rate and TTF (time to treatment failure) were higher with AT vs single agents
METASTATIC BREAST CANCER TREATMENT
Chemotherapy
Combination vs. sequential single agents
Docetaxel vs docetaxel + capecitabine
Response rates were higher with combination
TTP higher with combination
OS higher with combination
METASTATIC BREAST CANCER TREATMENT
Chemotherapy
Combination vs. sequential single agents
Paclitaxel vs paclitaxel + gemcitabine
Response rates higher in combination
OS higher in combination
Increased toxicity with combo
- Anemia
- Neutropenia
- Thrombocytopenia
- Neuropathy
- Fatigue
METASTATIC BREAST CANCER TREATMENT
Chemotherapy
Combination vs. sequential single agents
Paclitaxel vs paclitaxel + gemcitabine
Response rates higher in combination
OS higher in combination
Increased toxicity with combo
- Anemia
- Neutropenia
- Thrombocytopenia
- Neuropathy
- Fatigue
METASTATIC BREAST CANCER TREATMENT
Chemotherapy
Preferred Agents
- Doxorubicin/Doxil
- Paclitaxel
- Capecitabine
- Vinorelbine
- Gemcitabine
- Eribulin
- Cisplatin or Carboplatin
- Pembrolizumab + chemo (TNBC and PD-L1)
- Sacituzumab govitecan-hziy (TNBC)
METASTATIC BREAST CANCER TREATMENT
Chemotherapy
Anthracyclines
Doxorubicin vs Doxil
- Median PFS and OS similar between Doxil and Doxorubicin
Cross-resistance with anthracyclines
- Doxorubicin pretreated patients may respond to Doxil
- Conversions for calculating cumulative dose have not been established but Doxil appears to be LESS cardiotoxic