breast cancer

risk factors of breast cancer

-female

-older age

-estrogen exposure

-lifestyle: alcohol, physical activity, obesity, dietary fat intake

-thoracic radiation

-benign breast disease

-genetics

-family history

who should get risk reduction

-known genetic predispostion or pedigree suggestive of genetic predispostition

-personal history of LCIS or strong family history

-gail model 5 year breast cancer risk of >/= 1.7%

-and life expectancy over 10 years

lifestyle modifications for risk reduction for breast cancer

-exercise

-decreased alcohol consumption

prophylactic mastectomy +/- bilateral oophorectomy

preferred for germline mutations at high risk of breast cancer

premenopausal pharmacotherapy risk reduction

tamoxifen

post menopausal pharmacotherapy risk reduction

raloxifene or aromatase inhibitors (exemestane and anastrozole)

general treatment principles of breast cancer

-surgery

-chemotherapy

-targeted therapy

-hormonal therapy

-radiation

sentinel lymph node biopsy (SLNB)

-only if clinically negative axillary lymph nodes on ultrasound

-sentinel lymph node is the first lymph node that receives lymph drainage from tumor

-if positive, may consider ALND

axillary lymph node dissection (ALND)

-more invasive

-higher rates of morbidity

-preferred if large tumors

most common type of breast cancer

HR+/HER2-

what is triple negative breast cancer

Negative for estrogen receptor, progesterone receptor, and HER2 receptor

hormone receptor positive (HR+)

estrogen receptor positive/progesterone receptor positive

HER2 receptor positive (HER2+) testing

-use IHC to scale staining level

-3+ -HER2+

-1+ to 2+ will send for FISH testing

FISH (fluorescence in situ hybridization)

fluorescent dye to dye DNA associated with the HER2 mutation

lobular carcinoma in situ

-abnormal cells found in the lobules of the breast

-diagnosed by biopsy

-goal to cure

-10 year risk of developing breast cancer

treatment of lobular carcinoma in situ

-observation

-endocrine therapy

-surgery

ductal carcinoma in situ

-breast cancer at its earliest stage before the cancer has broken through the wall of the milk duct

-goal to cure

treatment of ductal carcinoma in situ

-surgery (lumpectomy vs mastectomy)

-radiation

-endocrine therapy

locally advanced breast cancer treatment

-diagnosis biopsy

-goal to cure

treatment of locally advanced breast cancer treatment

-surgery (breast-conserving therapy or mastectomy)

-radiation

-neoadjuvant or adjuvant chemo

advantages of neoadjuvant chemo

-shrinks tumor

-allows assessment of chemo effectiveness during surgery

indications of neoadjuvant treatment

-inflammatory breast cancer

-triple negative breast cancer

-patient wants surgery but is not a candidate at presentation

-patient medically unfit for surgery

-inoperable disease

triple negative breast cancer chemo

-regimens are often anthracycline based doublet

-AC

-AC -> T

-TC

-dose dense AC -> T

AC chemotherapy

doxorubicin and cyclophosphamide every 21 days

AC -> T chemotherapy

AC followed by paclitaxel

TC chemotherapy

docetaxel and cyclophosphamide

what chemotherapeutic agent has a cumulative lifetime dose limit due to cardiotoxicity and needs a baseline ECHO

doxorubicin

anthracyline chemotherapeutics

doxorubicin

adverse effects of cyclophosphamide

myelosuppression, mouth/tongue sores, N/V

severe toxicities of cyclophosphamide

hemorrhagic cystitis (high dose >1200 mg/m2), secondary malignancies, reproductive impairment

adverse effects of docetaxel

infusion reaction, AST/ALT elevation, N/V, edema, dermatologic reactions

what do we premedicate with 1 day prior to docetaxel administration to help prevent edema and dermatologic reactions

dexamethasone

true or false: paclitaxel can be given alone, in combination with other therapies, or after AC

true

adverse effects of paclitaxel

infusion reaction, AST/ALT elevation, N/V, peripheral neuropathy

what do we premedicate with prior to paclitaxel administration

steroid, APAP, and H2 and H1

what breast cancer can we add immunotherapy to up front

triple negative

what immunotherapy is added to neoadjuvant treatment for triple negative breast cancer

pembrolizumab (keytruda)

for premenopausal women with HR+/HER2- breast cancer where are we stopping estrogen

at the receptor

what chemotherapeutic agents can and cannot be used for premenopausal women with HR+/HER2- breast cancer

-LHRH inhibitors

-cannot use aromatase inhibitors

what is our therapeutic goal for postmenopausal women with HR+/HER2- breast cancer

stop androgen conversion to estrogen

what chemotherapeutic agents do we use in postmenopausal women with HR+/HER2- breast cancer

SERM, AIs

endocrine therapy options for premenopausal women with HR+/HER2- breast cancer

tamoxifen for 5 years and could add 5 more if still premenopausal

endocrine therapy options for postmenopausal women with HR+/HER2- breast cancer

AI for 5 years

SERM

selective estrogen receptor modulator

examples of SERMs

Tamoxifen

Raloxifene

adverse effects of tamoxifen

hot flashes, bone loss, stroke, VTE

drug interaction of tamoxifen

CYP2D6 inhibitors

examples of aromatase inhibitors

Letrozole

Anastrozole

Exemestane

adverse effects of aromatase inhibitors

-hot flashes

-bone loss

-arthralgias

-VTE

what supplement should be taken if taking tamoxifen

calcium + vitamin D

what CDK 4/6 inhibitor can be added as endocrine therapy for high risk HR+/HER2- breast cancer

abemaciclib and ribociclib

OncotypeDx

guides decision on adjuvant chemotherapy in HR+/HER2-, node negative disease

based on OncotypeDX for HR+/HER2- breast cancer, we will only give chemo if recurrence score is ______ for premenopausal women

>16

based on OncotypeDX for HR+/HER2- breast cancer, we will only give chemo if recurrence score is ______ for postmenopausal women

>26

adjuvent chemo for (HR +/-)/ HER2+

chemo + anti-HER2 therapy + endocrine therapy

anti-HER2 therapies

-trastuzumab

-pertuzumab

-ado-trastuzumab emtansine

-fam-trastuzumab deruxtecan

drug class of trastuzumab

monoclonal antibody, HER2 targeting

adverse effects of trastuzumab

-infusion reactions

-cardiotoxicity

drug class of pertuzumab

-mAb

-overcomes resistance from trastuzumab

adverse effects of pertuzumab

-infusion reactions

-cardio toxicity

-diarrhea

what monoclonal antibody for breast cancer is never given as monotherapy

pertuzumab

neoadjuvant chemo for (HR +/-)/ HER2+

-6 cycles

-docetaxel

-cyclophosphamide

-trastuzumab

-(+/-) pertuzumab

adjuvant chemo for (HR +/-)/ HER2+

-1 year of HER2 directed

-trastuzumab

-(+/-) pertuzumab

class of ado-trastuzumab emtansine

antibody drug conjugate, HER2 targeting

indication of ado-trastuzumab emtansine

residual disease (surgical specimen) after neoadjuvant treatment

adverse effects of ado-trastuzumab emtansine

-infusion reactions

-cardiotoxicity

-peripheral neuropathy

ado-trastuzumab emtansine brand name

Kadcyla

fam-trastuzumab deruxtecan brand name

Enhertu

indications of Enhertu

-invasive breast - residual disease after surgery

-metastatic breast - first line with pertuzumab and 2nd line monotherapy

-HER2+ gastric and lung cancer

black box warning of Enhertu

interstitial lung disease and pneumonitis

adverse effects of Enhertu

-cardiotoxicity

-peripheral neuropathy

-neutropenia

-diarrhea

what drug is considered an extended adjuvant

neratinib

MOA of neratinib

PO pan inhibitor of HER family of tyrosine kinase

indications of nertinib

HER2+ with hormone positive and/or node positive disease

adverse effects of nertinib

diarrhea

what prophylactic is required for neratinib

loperamide

for triple negative breast cancer, what do we do when residual disease is found in a surgical specimen

-evaluate treatment plan

-ado-trastuzumab emtansine

-capecitabine

-olaparib

for HR+/HER2+ breast cancer, what do we add when residual disease is found in the surgical specimen

add ado-trastuzuma emtansine or fam-trastuzumab deruxtecan