Breast Cancer Flashcards
What are some NON-MODIFIABLE risk factors for developing breast cancer?
Female*
Older > 50*
White
Family hx
Genetics
Breast changes found on biopsy
Radiation < 30 yo
High breast density
Late menopause/early menarche
What are some MODIFIABLE risk factors for developing breast cancer?
No pregnancies/first child at older age
Post-menopausal hormone replacement
Postmenopausal obesity
Physical inactivity
EtOH
Where do breast cancers develop within the breast?
Lobular and ductal epithelium = proliferative abnormality
Local (IN-SITU) breast cancer has not penetrated membrane, is contained
May become invasive
Which is more common, ductal or lobular breast carcinoma? Which is more likely to progress from in-situ to invasive?
Ductal is both more common and more likely to become invasive
How do invasive ductal and lobular breast carcinomas differ in presentation and locations for metastasis?
Invasive ductal carcinoma is the signature “lump” in breast, metastasis to bone, liver, lung, brain
Invasive lobular carcinoma is a general thickening of the breast, metastasis to leptomeninges, peritoneum, GI, gonads
What are special other types of breast cancer from ductal or lobular? Do they have better or worse prognoses?
Medullary
Mucinous (colloid)
Tubular
Rarer, have better prognoses
What is the presentation of INFLAMMATORY breast cancer? How does this evolve from normal breast cancer?
Signs: skin redness, edema, warmth, hardening of tissue
Cancer cells migrate to dermal lymphatics
Often rapid progression, thus poor prognosis
Who should be screened for breast cancer? (Average risk people)
All women should have “breast awareness”
Women 25-39 = clinical breast exam q1-3 years
Women ≥ 40 = clinical breast exam and mammogram every year
What is the general clinical presentation of breast cancer?
Asymptomatic, non-mobile lump, usually painless
Occasional breast or nipple pain
Rarely nipple discharge, retraction, dimpling
Advanced: redness warmth, edema
Metastatic - swollen lymph nodes, sx dependent on location of metastasis
What diagnostics should be conducted to confirm breast cancer?
History and physical exam
Bilateral mammogram
Breast ultrasound
Breast biopsy
May consider bloodwork
What FIVE factors affect predicted prognosis of breast cancer?
Tumor size
Lymph node involvement status
Tumor grade (differentiation, like Gleason score)
- Grades 1-3 from normal cell to fully abnormal looking cell
Ki67 index (measures rate of cell division)
Lymphovascular invasion
What are the THREE breast cancer biomarkers?
Hormone receptor markers:
Estrogen Receptor (+) [ER]
Progesterone Receptor (+) [PR]
Predicts how tumor will respond to hormone therapy
HR (+) tumors are slower growing and less deadly
HER2 gene
Control breast tissue growth, division, repair
If overamplified = more rapaidly growing and aggressive
Triple negative cancers (~15%)
- grow quickly but are chemo-sensitive
How is breast cancer staged?
TNM staging
+
Biomarkers *ER, PR, HER2)
Early stage = 0.1.2 [CURE]
Locally invasive = 3 [CURE]
Metastatic = 4
What is the treatment of in-situ lobular breast carcinoma?
Monitoring
What is the treatment of in-situ ductal breast carcinoma?
Lumpectomy + Radiation
Mastectomy
Hormone receptor (+)? = consider endocrine therapy
What are some surgical options for invasive breast cancers?
Lumpectomy + radiation
Mastectomy +/- radiation
& chemo/target/endocrine therapy
Why do we use chemotherapy even after mastectomy or lumpectomy?
Systemic chemo can destroy any lingering cancer cells to prevent relapse (mop up)
What are the two paths for invasive breast cancer treatment? What if they are Hormone (+)? Hormone (-)?
General Path:
1. Surgery -> adjuvant chemo -> +/- RT -> +/- endocrine
2. Neoadjuvant chemo -> surgery -> +/- RT -> +/- endocrine
HR (+):
1. ER/PR(+) AND HER2(+) = chemo + HER2 therapy + endocrine therapy
2. ER.PR(+) BUT HER2(-) = chemo + endocrine therapy
HR(-):
1. ER/PR(-) AND HER2(+) = chemo + HER2 therapy
2. ER/PR(-) AND HER2(-) [triple negative] = chemo only!
What SIZE should a breast cancer tumor be to qualify for chemotherapy?
Since chemo is toxic, limit!
>1 cm = give chemo
0.6 - 1 cm = consider chemo
≤0.5 cm = AVOID
What is the Oncotype DX tool?
Tumor biopsy tests for 26 genes, directs prognosis and relapse risk in HER2 (-) BUT ER/PR(+) cancers.
Score 0-100, higher is worse
Divide into:
Post-menopausal
<26 = endocrine therapy only, no chemo benefit
≥26 = chemo followed by endocrine therapy
Pre-menopausal Node (-)
≤15 = no chemo benefits
16-25 = chemo followed by endocrine OR ovarian suppression + endocrine
≥26 = chemo followed by endocrine therapy
Pre-menopausal Node (+) [N1 score]
<26 = chemo followed by endocrine OR ovarian suppression + endocrine
≥26 = chemo followed by endocrine therapy
What chemo do we use for ER/PR (+/-) & HER2(-) breast cancer?
Dose-dense doxorubicin/cyclophosphamide q2wk x4 doses + (paclitaxel q2wk x 4 doses OR paclitaxel qweek x 12 doses)
OR
Docetaxel/cyclophosphamide q2wk x 4-6 doses
What chemo do we use SPECIFICALLY for ER/PR (-) & HER2(-) breast cancer?
Neoadjuvant:
Pembrolizumab q3wk x 4 doses + paclitaxel/carboplatin qweek x 12 doses
Then Pembrolizumab + doxorubicin/cyclophosphamide q3wk x 4 doses
Adjuvant:
Pembrolizumab q3wk x 9 doses
What chemo do we use for HER2(+) breast cancer?
Docetaxel/carboplatin/trastuzumab +/- pertuzumab q3wk x 6 doses
OR
Paclitaxel + trasutzumab qweek x 12 doses
Only give pertuzumab if: ≥T2 or N1 with high recurrence risk
Post-chemo - continue trastuzumab OR trastuzumab/pertuzumab for 1 year
What drugs are HER2-specific and downregulate HER2 expression?
Trastuzumab, Pertuzumab
What is a major AE with docetaxel? How can we prevent this?
Peripheral edema
- premeditate with dexamethasone
What are key counseling points for doxorubicin?
Cardiotoxicity (recall)
RED urine/secretion discoloration
Increased secondary malignancies
Blistering, extraspatial leakage
What are some key counseling points for cyclophosphamide?
Hemorhagic cystitis (significant bladder irritation)
Sterility
What are some key counseling points for trastuzumab/pertuzumab?
Cardiotoxicity [CHF, ventricular dysfunction]
- reversible
Diarrhea (pertuzumab)
Infusion rxns
How does the location of estrogen production vary between pre and post menopausal women?
Pre-menopause = ovaries
Post-menopause = via aromatase (concentrated in peripheral adipose tissue)
What drug is primarily used in endocrine therapy for premenopausal breast cancer patients w/ ER/PR(+)? What kind of CYP interactions should we be cautious of?
Tamoxifen - prodrug of hepatically active endoxifen
AVOID strong CYP2D6 inhibitors required for prodrug conversion!
Ie. fluoxetine, paroxetine, bupropion
Citalopram, escitalopram, venlafaxine, mirtazipine are permitted
What adjuvant endocrine therapy should PRE-MENOPAUSAL women use for breast cancer?
- Tamoxifen
- Aromatase inhibitor + ovarian suppression (simulates post-menopause)
What adjuvant endocrine therapy should POST-MENOPAUSAL women use for breast cancer?
- Aromatase inhibitor
- Consider Tamoxifen
How is ovarian suppression achieved?
Oophorectomy
LHRH agonists (recall from prostate cancer)
- Goserelin 3.6 mg SQ month
- Leuprolide 3.75 mg IM q28 days
What are important counseling points about risks with tamoxifen in breast cancer treatment? What are some AEs?
AES:
menopausal sx (night sweats, vaginal dryness, hot flashes)
Menstrual changes
Risks:
Uterine/endometrial cancer
VTE/stroke
Avoid in pregnancy! (Avoid COCs/POP/hormonal IUD)
What are important counseling points about risks with aromatase inhibitors in breast cancer treatment? What are some AEs?
AEs:
menopausal sx (night sweats, vaginal dryness, hot flashes)
Musculoskeletal sx (arthralgia, joint stiffness, bone pain)
- use acupuncture
Risks:
Osteoporosis & fractures
High cholesterol
CVD risk
What are some of the aromatase inhibitors we use in endocrine therapy?
Anatrazole
Letrozole
Exemestane
What are some additional adjuvant therapies for breast cancer patients who have tried chemo/surgical/endocrine therapies?
Capecitabine
- for TRIPLE NEGATIVE (HER2-, ER/PR-) who did not have successful neoadjuvant therapy
Ado-trastuzumab
- HER2+ who did not have successful neoadjuvant therapy
Neratinib
- HER2+ who received chemo + trastuzumab, used in HIGH RECURRENCE RISK patients! Use for extra year
- DIARRHEA (use loperamide)
Olaparib (recall from prostate cancer)
- BRCA mutation, high risk HER2-
Abemacimib
- ER/PR+, HER2- high risk
- Extends chemo x2 years, must be given in combo w endocrine
Zoledronic acid
- Post-menopausal pts to decrease bone loss
What treatments should be used in METASTATIC, ER/PR(+) HER2(-) breast cancer?
Cyclin-dependent kinase inhibitor (Palbociclib, Ribociclib, Abemaciclib)
Use in combo w aromatase inhibitor or fulvestrant
- Abemaciclib may be monotherapy after endocrine before chemo
AEs: fatigue, neutropenia, anemia, alopecia
- Monitor liver function & QTc prolongation (ribociclib)
- Monitor liver function & SCr (abemaciclib)
On a 21 day on/7 day off cycle
Everolimus
Use combo w exemestane or fulvestrant when aromatase inhibitors fail
AEs: metabolic, pneumonitis, stomatitis, rash
Alpelisib
for ER/PR(+), HER2(-), PIK3CA mutations
Use in combo w fulvestrant
AE: hyperglycemia, skin rash, diarrhea, nausea, fatigue, increased SCr
When a patient has METASTATIC breast cancer, when should chemo be initiated?
Failure to multiple endocrine therapies
Visceral crisis
Pt is symptomatic
Pt decides they want it
Requires good performance status
Duration of chemo will decrease with each cycle
What kinds of metastatic breast cancer patients would qualify for combination chemotherapy?
Very high performance status, at an early stage of treatment for rapid control
What is first line treatment for METASTATIC, HER2(+) breast cancer? What are other options if this doesn’t work?
1st line:
- Pertuzumab + trastuzumab + docetaxel
- Pertuzumab + trastuzumab + paclitaxel
Alternatives:
- Fam-trastuzumab deruxtecan-nxki (Ab-drug conjugate)
- Ado-trastuzumab emtansine (Ab-drug conjugate)
- Tucatinib + trastuzumab + capecitabine
What are THREE Ab-Drug conjugates we may use in metastatic breast cancer?
Fam-trastuzumab deruxtecan-nxki
Ado-trastuzumab emtansine
Sacituzumab govitecan-hziy
What two agents may be considered in patients with bone metastases from metastatic breast cancer?
Bisphosphonates:
Zoledronic acid
Pamidronate
(Helps prevent skeletal-related events)
AEs: osteonecrosis of the jaw (regular dental follow-up), arthralgia, fever
Must dose-adjust in renal dysfunction
Denosumab
AEs: hypocalcemia, fatigue, dyspnea
no renal adjustments
What are some tumor markers to recognize in breast cancer? (3)
Carcinoembryonic antigen (CEA) [nonspecific]
Cancer antigen 15-3 (CA15-3) [breast cancer specific]
Cancer antigen 27.29 (CA 27.29) [breast cancer specific]
*mainly useful in metastatic cancer to monitor treatment response]
What are some important survivorship issues to consider in breast cancer patients? (Aka QoL)
Hot flashes
- treat w/ gabapentin or venlafaxine
Sexual issues
- treat w/ lubricants or moisturizers
- AVOID topical estrogens!
Infertiflity
- caused by chemo/endocrine therapy, discuss w patients
Lymphedema
- treat w/ compression garments, physical therapy
Osteoporosis
- Screen w DEXA scans, counsel on vitamin intake
Neuropathy
- caused mostly by taxanes
- consider duloxetine
Cardiotoxicity
- doxorubicin
Secondary malignancies
- from topoisomerase inhibitors (topotecan), radiation, tamoxifen
