Breast cancer Flashcards
Cutoffs for HER2 positivity and ER positivity?
HER2 by IHC is 3+ and by FISH is 2.
ER is >1%
What is the ddACT schedule?
AC every two weeks x 4 cycles followed by taxol every two weeks x four cycles with GCSF or every week x 12 weeks without GCSF (better tolerated every week)
How does neoadjuvant chemo affect PFS and OS in breast cancer?
It doesn’t compared to adjuvant.
Work-up for early stage breast cancer?
No additional studies needed
Side effects of paclitaxel
interstitial pneumonitis within days to weeks of receiving a taxane.
noncardiogenic pulmonary edema
With appropriate premedication, the incidence of infusion reactions is approximately the same (1 to 3 percent) whether paclitaxel is administered over 24, three, or one hour [81,82]. However, the incidence may be higher with infusion times under one hour [83]. Even with appropriate premedication, mild reactions (skin rash, flushing) still occur in a substantial number of patients.
Paclitaxel is formulated in Cremophor,
Give a steroid to prevent a rash.
FYI give at much lower dose for breast cancer.
What are the indications for neoadjuvant treatment in breast cancer?
Used mostly in TNBC or HER2+, ER neg disease
T2 lesion (>2cm) or N1
T2 is greater than 2cm
We give it to downstage
Metastatic breast cancer - rules for biopsying?
Always biopsy site of met as may have discordant disease.
20%!
Neoadjuvant chemo and complete response is more common in what group breast cancer?
More commmon in triple negative and and HER2+.ER-
for ddACT, what meds do you give with it?
ddAC -sestron, prepitant and steroid. FOr T give steroid
Micrometastases or ITCs (isolated tumor cells) in lymph nodes in breast cancer
IGNORE THEM!!!
Extended estrogen therapy benefits and downsides in breast cancer?
It is associated with better DFS but worse bone side effects. Consider it for high risk disease.
Who benefits the most from ovarian suppression?
Less than 35 year old woman and/or aggressive disease. high oncotype or LN+
Switching AI and/or tam - is it OK?
Yes. BIG 1-98
Side effects of tamoxifen
DVT, endometrial hyperplasia/ca, increased bone density. NO ROLE for cyp2D6 testing.
What antidepressants are ok to use with tamoxifen?
venlafaxine and citalopram
AI side effects
osteoporosis and bone pain
Tam + ovarian suppression
NEVER DO IT
older lower risk patient who is not menapausal and ER positive disease?
just give tam!
oncotype cutoffs
> 10 or >31
When to give chemo and RT and AI
Never give chemo and hormones or chemo RT at the same time.
small, node-negative, human epidermal growth factor receptor type 2 (HER2)–positive breast cancers?
Adjuvant TH based upon small single arm phase two trial (tolaney)
or
ACTH for T1
Aphinity trial and neosphere trials
Adjuvant: DFS benefit for HP over H for high risk T2 or greater or N1 or greater. But small.
Neoadjuvant: same thing
HERA trial
antiher2 therapy lasts for 1 year
What do you do if EF drops below 50% during HP?
Hold it, wait one month and recheck
Adjuvant TDM1 or lapatinib
NO ROLE
HER2+ ER+
combine ER with HER2 when chemo is over
TAILORRX
ongoing <10 had 98% OS
RXponder
LN+ trial for oncotype
Trial for premenapausal woman
NSABP-14 tam x 5 yrs
Trial for postmenapausal AI>tam
ATAC and BI1-98
Trial for AI+OS
SOFT/TEXT
Trial for 10>5
MA.17R
First line therapy for metastatic TNBC?
Weekly paclitaxel. Or adriamycin. Never give dose dense or combo in metastatic setting.
Eribulin in breast cancer?
2nd/3rd line after anthracycline and taxane progression.
Liver clearance
GC- VITAL G-gem C-cap V-vinca I-tecans T-axane A-anthracycline L-liver
PARP inhibitors in metastatic breast cancer?
Olaparib approved in HER2 negative BRCA + metastatic disease. OLYMPIAD
mechanism for neratinib
TKI against HER2 in people with early stage breast cancer in which HER2 is over expressed, after the person receives treatment with trastuzumab.
lapatinib mechanism
dual tyrosine kinase inhibitor which interrupts the HER2/neu and epidermal growth factor receptor (EGFR) pathways.[2] It is used in combination therapy for HER2-positive breast cancer.
T-DM1 mechanism
Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate . onsisting of the monoclonal antibody trastuzumab (Herceptin) linked to the cytotoxic agent emtansine (DM1).
Trastuzumab alone stops growth of cancer cells by binding to the HER2/neu receptor, whereas DM1 enters cells and destroys them by binding to tubulin..
Pertuzamab MOA
humanized monoclonal antibody that binds to the extracellular domain II of HER2. Its mechanism of action is complementary to trastuzumab, inhibiting ligand-dependent HER2–HER3 dimerization and reducing signaling via intracellular pathways such as phosphatidylinositol 3-kinase
fulvestrant MOA
selective estrogen receptor degrader (SERD) and was first-in-class to be approved.[3] It works by binding to the estrogen receptor and destabilizing it, causing the cell’s normal protein degradation processes to destroy it
Pertuzamab major side effect
diarrhea
TDM1 major side effect
neuropathy and neutropenia
Palbociclib major side effect
neutropenia
EVerolimus major side effect
diarrhea
Lapatinib major side effect
diarrhea
Eribulin major side effect
neutropenia and neuropathy
First line for metastatic ER+, HER2 neg breast cancer?
AI+CD4/CD6 Paloma-2 trial
Prior endocrine therapy within 1 year is
cutoff for switching to next line like SERD if develops MBC
2nd line therapy in ER+ MBC post AI
if did not receive CD4/6 can do fulvestrant + CDk4/6 Paloma 3
TAM/AI sensitive mbc
> 12 months since exposure. CD4/6+ AI–>SERD–>single agent chemo
can also do everolimus + exemenstane.
TAM/AI insensitive mbc
> 12 months since exposure. CD4/6+ fulvestrant(serd)->single agent chemo
single agent CD4/6
approved but only use in heavily pretreated population
predicts lack of response to AI in breast cancer
ESR1 mutation
Bone agents
always prescribe denosumab or bisphosphonate for ER+ MBC with bone mets
metastatic ER+, HER2+ disease first line
THP x 6 f/b HP maintenance
CLEOPATRA study. 56 mo OS benefit
Second line for metastatic HER2+ disease
TDM1
EMILIA trial TDM1>cape/lapatinib for those progressed on H (no data for post THP)
3rd line anti-her2
cape/lapatinib offen given for brain mets (LANDSCAPE trial)
otherwise give nonantracycline + herceptin
for ER/HER2+ THP–>HP maintenance + AI
When is mastectomy indicated?
History of chest RT, multifocal disease
When can we avoid adjuvant RT??
if >70 years old with T1N0 dz.
CALGB9343
When can you avoid ALND?
T1 or T2 s/p lumpectomy with only 1-2 +SLN and getting systemic + RT
ACOSOG Z11.
Need to be clinically node negative.
Indication for radiation after mastectomy??
> 4 lymph nodes = N2 disease
or peud d orange disease
standard for inflammatory breast cancer or peu d orange
NACT –> mastectomy with ALND –> RT
THIS IS A CLINICAL DIAGNOSIS
Chemoprevention
SERM - tam or raloxifene
Tam is better but raloxifene has decreased risk of endometrial cacer so if still has uterus use raloxifene in post menopausal women
when to do MRI for surveillance monitoring
if high risk - genetics, dense breasts, prior RT
if mastectomy, no imaging is needed
male breast cancer
almost always ER+. give tam for localized or metastatic disease
BRCA1 vs 2
BRCA 1 more likely TNBC
BRCA2 ER+
Bilateral masetcomy and BSO at age 35 or after childbearing
testing ALL BC<50, TNBC<60, male BC
Papillary breast lesions management
Recent studies demonstrate a 3 to 33% chance that atypia, DCIS or invasive carcinoma will be identified at excision. Given this risk, complete excision should be considered the standard of care. Studies show that larger or more core biopsies can decrease the risk of finding additional pathology but there remains a risk of upgrading at excision.
The risk of subsequent cancer for intraductal papilloma is low (2 fold over general population risk). Tamoxifen would not be generally recommended for this level of risk. Combined hormone replacement therapy could be stopped, given the risk of breast cancer associated with use, however this is not a replacement for excision.
Stage 2 perimenopausal
Do five yrs tam f/b five years AI because stage 2 and not stage 1.
Pure tubular cancers
(pTC) are rare, representing about 1 to 2% of all breast cancer. PTC is associated with an excellent prognosis with low likelihood of lymph node positivity and distant metastasis. PTC’s are well differentiated and commonly highly estrogen receptor and progesterone receptor positive.
reduce the risk of contralateral breast cancer in women with a prior BRCA1 treated cancer
Tamoxifen has been shown to reduce the risk of contralateral breast cancer in women with a prior BRCA1 treated cancer. Raloxifene has been studied as a breast cancer chemo preventive agent only in postmenopausal women
leptomeningeal carcinomatosis (LC) in breast cancer
For patients with fixed neurologic deficits from bulky leptomeningeal disease (i.e., nodules greater than a few millimeters), initial radiotherapy to symptomatic sites is important, as intrathecal chemotherapy penetrates 3 mm or more into neoplastic tissue and is less effective than radiation therapy in alleviating or stabilizing fixed neurologic deficits. Radiation therapy may be followed by intrathecal chemotherapy or, in some cases, a systemic therapy that achieves therapeutic concentrations within the cerebrospinal fluid. Craniospinal irradiation is generally avoided due to excessive toxicities.
adriamycin toxicity
Age is an important risk factor for doxorubicin-related CHF after a cumulative dose of 400 mg/m^2, with older patients (age > 65 years) showing a greater incidence of CHF compared with younger patients (age < or = 65 years). The development of heart failure may occur at cumulative doxorubicin doses that are much lower than would be expected with doxorubicin alone in patients who received combination chemotherapy. Cardiomyopathy is reported when paclitaxel is combined with doxorubicin. Heart failure has developed in up to 20% of patients treated with paclitaxel plus doxorubicin although an increased incidence of cardiotoxicity was not seen in all studies.
PREDICT score
helpful estimate risk of recurrent disease.
