Breast cancer EXAM 2 Flashcards
Which receptors are relevant in breast cancer and determine the aggressiveness of the disease?
ER: estrogen receptor
PR: progesterone receptors
HER2: human epidermal growth factor receptor
Which breast cancer is the least aggressive and most aggressive, why?
least aggressive Luminal A
bc it still has functional ER, PR, and HER2 receptors
-well differentiated
-slow growing
most aggressive: triple negative: lost function of ER, PR, and HER2 amplified
What are the risk factors for breast cancer?
-Age
-female sex
-estrogen exposure
-genetics: BRCA1, BRCA2
-Environment: obesity, radiation
What are the risk factors associated with Estrogen exposure?
-Young age at menarche: < 12 years
-Older age at 1st birth: > 30 years
-Nulliparity (Nuns!)
-Older age at menopause: > 55 years
-Oral contraceptive use
more lifetime estrogen exposure !!!
Which genes are associated with a higher risk for breast cancer?
-BRCA1 (higher risk than BRCA2)
-BRCA2
-> repair genes (if mutated, less repairing)
also increase the risk of ovarian cancer
Why is adipose tissue a risk factor for breast cancer?
because it produces estrogen
-more estrogen means higher risk
Ductal (DCIS) and Lobular (LCIS) carcinoma in situ are considered invasive or non-invasive?
non-invasive
in situ= in place; they do not have the ability to invade surrounding tissues
How would a patient with breast cancer commonly present?
-painless breast lump: solid, solitary, unilateral, irregular, immobile
-asymptomatic on mammography screening
less common: pain, nipple discharge, redness, warmth (often aggressive cancer)
Most women should be screened for breast cancer at what age?
NAPLEX
at age 40
earlier if present risk factors
Which protein in breast cancer cells is sign for aggressive breast cancer?
Ki-67
highly expressed during proliferation
Which hormone receptors indicate a poor prognosis for breast cancer?
-non-functional ER and PR
-also when it is spread in the lymph nodes
other factors:
<35 y: the younger, the more likely it is triple negative (aggressive)
-African-American
-large tumor size
Which stages of breast cancer are considered curable?
Stage I, II, III (stage 4 is incurable)
-use drugs
-use radiation
A patient’s breast cancer profile is hormonal positive: ER (+) and PR (+). Which type of drugs should be included for anticancer treatment?
Hormonal agents (always if ER or PR positive)
-SERMs (Tamoxifen)
-Aromatase inhibitors
A patient presents with HER2-amplified cancer cells. Which type of drugs should be included for anticancer treatment?
When is chemotherapy considered in breast cancer patients?
!!!
-if the cancer has spread into lymph nodes
-aggressive disease (example: triple negative)
What is the most appropriate approach to treat a patient with Stage I breast cancer?
Surgery
-may consider pre-therapy: HER2 if HER2 amplified or chemo
What is the most appropriate approach to treat a patient with Stage III breast cancer?
more likely to need Neoadjuvant therapy before surgery
What is the role of drugs in breast cancer?
!!!
drugs are not as important as surgery (bc it is a solid tumor that can be cut out)
-hormonal therapy is most important for ER or PR-positive disease
-targeted therapy (HER2, CDK 4/6 inhibitor)
-Chemotherapy
What is the 1st line drug for most hormone metastatic disease?
CDK 4/6 inhibitors
-palbociclib
-Ribociclib
-abemaciclib
Which hormones of the HPA axis stimulate estrogen production in the ovaries?
-GnRH (from the Hypothalamus)
-FSH (from pituitary glands)
(androgen from the adrenal gland is converted into estrogen too)
What are the toxicities of Tamoxifen (SERM) and AIs?
-Hot flashes, night sweats !!!
-arthralgia, myalgia (more with AIs)
-fractures
-thrombotic risk
What are the effects of Tamoxifen and Raloxifen in different tissues?
antiestrogenic in the breast
-estrogenic in the
bones: increases bone density
endometrium: endometrial growth, hyperplasia
blood: increased clotting factor (clotting risk), vasodilation
Which enzyme converts androgen to estrogen?
Aromatase
Name the Aromatase inhibitors (AIs).
-Letrozole
-Anastrozle
-Exemestane
What is the effect of using AIs only in patients who are premenopausal?
the body reacts and bumps up estrogen production,
cant use AIs only in premenopausal (positive feedback loop)
Why only in premenopausal??
bc in postmenopausal the body cant react bc no estrogen production from the hypothalamus
as monotherapy only in postmenopausal!!!
What is the dose of anastrozole and letrozole for breast cancer treatment? What is the brand name?
anastrozole (Arimidex): 1 mg PO daily
letrozole (Femara): 2.5 mg PO daily
What is the dose of exemestane and tamoxifen for breast cancer treatment? What is the brand name?
exemestane (Aromasin): 25 mg PO daily
tamoxifen (Soltamox): 20 mg PO daily
What are the main differences between Tamoxifen and AIs?
Tamoxifen is used in pre and postmenopause; AIs are only in postmenopausal
What is the most appropriate drug for a 65 yo postmenopausal patient to treat breast cancer?
Aromatase inhibitor - can be used as monotherapy for postmenopausal patients
(more efficacy than tamoxifen)
A 60 yo patient needs treatment for breast cancer. She is postmenopausal and complains about hot flashes.
Which drug is more appropriate for treatment, AI or tamoxifen?
What if they have complained about joint pain (arthralgia) or myalgia?
What if they had a history of a broken leg?
!!!
for hot flashes: go with AI (fewer side effects)
for arthralgia: go with tamoxifen
for bone fractures: go with tamoxifen (AI causes more bone fractures since it blocks the last source of estrogen in postmenopausal)
The risk for thrombosis is higher in tamoxifen or Aromatase inhibitors?
Tamoxifen
(estrogenic effect in the blood -> risk for blood clots)
How is Tamoxifen metabolized to its active metabolite?
CYP2D6
(1st converted into isoform via CYP3A4)
-may check genetics
-cautious about CYP2D6 inhibitors
What is the active metabolite of Tamoxifen?
endoxifen
What are common strong CYP2D& inhibitors?
Strong:
-Fluoxetine
-Paroxetine
-Bupropion
Which class of drugs are involved in the HPA axis and used to reduce estrogen production in breast and prostate cancer? Explain the MOA.
GnRH analogs
they initially stimulate LH and FSH release -> more estrogen release
-negative feedback causes a reduction in estrogen
What are two indications of GnRH analogs?
-combination therapy with AIs for breast cancer (or prostate cancer)
-fertility preservation during chemo (chemo can cause premature ovarian failure)
What are the GnRH analogs?
Goserelin
Leuprolide
often used in combi with AIs (blocks the negative feedback loop caused by AIs)
What is the brand name of Tamoxifen?
Soltamox
The use of chemotherapy in breast cancer depends on what?
-Tumor size > 1 - 2 cm or lymph node spread
-OncoTypeDx recurrence score (TAILOR Rx Study*)
What is the recommended duration of hormonal treatment in patients with breast cancer?
at least 5 years (10y are better)
Who benefits from adjunctive therapy?
if high risk for recurrence
-present in Lymph nodes
-hormonal receptor (-), TNBC
-OncoTypeDx score
Which patients is neoadjuvant therapy commonly used?
to make the surgery easier
-inflammatory breast cancer
-large tumor size
it gives feedback if the chemo works (tumor-shrinking)
-more likely used with HER2 in HER2-amplified cancer (works so well)
-more likely used in triple-negative breast cancer
Risk factors for recurrence
-young age <35
-large tumor size
-ER/PR negative, TNBC
-poor grade, Grade 3 poorly differentiated
-spread in lymph nodes
-high OncotypeDx score
What is the MOA of trastuzumab?
prevents dimerization and activation of HER2
How do trastuzumab and Pertuzumab work in combination?
Pertuzumab binds on a different site on HER2
-dual HER2 blockade works better than a single blockade
Which intervention is considered in BRCA1-positive patients?
double sided Mastectomy
Metastatic Disease Treatment
CDK inhibitors + hormonal therapy (if ER or PR positive) + bone modifying agents to prevent SRE
bone-modifying agents: +
-Denosumab (Xgeva)
-zoledronic acid (Zometa)
What is the side effect profile of CDK inhibitors?
mini-chemo
some:
-myelosuppression
-mucositis
-N/V
-alopecia
Which drugs are considered for Bone metastasis?
Bisphosphonates
-Zoledronic acid: 4 mg IV q6h (prostate cancer with mets)
-Pamidronate (Aredia)
Patients treated with Zoledronic acid or Pamidronate need which supplements?
500 mg Calcium
400 IU Vitamin D
unless Ca is high
What is the brand name of Zoledronic acid?
Zometa
What is the brand name of Pamidronate?
Aredia
What is the brand name of Paclitaxel and Docetaxel?
Paclitaxel: Taxol
Docetaxel: Taxotere
What is the brand name of Vinorelbine?
Navelbine
What is the brand name of Gemcitabine?
Gemzar
What is the brand name of Capecitabine?
Xeloda
What is the brand name of Liposomal doxorubicin?
Doxil
What is the brand name of Nanoparticle albumin-bound paclitaxel?
Abraxane
What is the brand name of Eribulin?
Halaven
What is the brand name of Ixabepilone?
Ixempra
Which premeds should you use for Paclitaxel?
REMINDER
-dexamethasone
-dipehnhydramine (benadryl)
-H2RA
Which drugs are used to treat patients with BRCA1 mutations?
PARP inhibitor (-par)
-olaparib
-niraparib
What is the side effect profile of PARP inhibitors?
-myelosuppression
-nausea
-risk of secondary leukemias
What are the treatment options to prevent cancer?
-Tamoxifen: 20 mg daily for 5 years
-Raloxifene
-Aromatase inhibitors
-bilateral mastectomies
-bilateral oophorectomies
benefits are less than adjuvant therapy though
What are the risks of using tamoxifen for breast cancer prophylaxis?
-VTE (estrogenic in the blood)
-endometrial cancer (estrogenic in the endometria)
