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Crit Care, Oncology & Hematology > Breast Cancer > Flashcards

Breast Cancer Flashcards

1
Q

What are some NON-MODIFIABLE risk factors for developing breast cancer?

A

Female*
Older > 50*
White
Family hx
Genetics
Breast changes found on biopsy
Radiation < 30 yo
High breast density
Late menopause/early menarche

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2
Q

What are some MODIFIABLE risk factors for developing breast cancer?

A

No pregnancies/first child at older age
Post-menopausal hormone replacement
Postmenopausal obesity
Physical inactivity
EtOH

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3
Q

Where do breast cancers develop within the breast?

A

Lobular and ductal epithelium = proliferative abnormality
Local (IN-SITU) breast cancer has not penetrated membrane, is contained
May become invasive

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4
Q

Which is more common, ductal or lobular breast carcinoma? Which is more likely to progress from in-situ to invasive?

A

Ductal is both more common and more likely to become invasive

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5
Q

How do invasive ductal and lobular breast carcinomas differ in presentation and locations for metastasis?

A

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

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6
Q

What are special other types of breast cancer from ductal or lobular? Do they have better or worse prognoses?

A

Medullary
Mucinous (colloid)
Tubular
Rarer, have better prognoses

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7
Q

What is the presentation of INFLAMMATORY breast cancer? How does this evolve from normal breast cancer?

A

Signs: skin redness, edema, warmth, hardening of tissue
Cancer cells migrate to dermal lymphatics
Often rapid progression, thus poor prognosis

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8
Q

Who should be screened for breast cancer? (Average risk people)

A

All women should have “breast awareness”
Women 25-39 = clinical breast exam q1-3 years
Women ≥ 40 = clinical breast exam and mammogram every year

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9
Q

What is the general clinical presentation of breast cancer?

A

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

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10
Q

What diagnostics should be conducted to confirm breast cancer?

A

History and physical exam
Bilateral mammogram
Breast ultrasound
Breast biopsy
May consider bloodwork

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11
Q

What FIVE factors affect predicted prognosis of breast cancer?

A

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

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12
Q

What are the THREE breast cancer biomarkers?

A

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

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13
Q

How is breast cancer staged?

A

TNM staging
+
Biomarkers *ER, PR, HER2)

Early stage = 0.1.2 [CURE]
Locally invasive = 3 [CURE]
Metastatic = 4

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14
Q

What is the treatment of in-situ lobular breast carcinoma?

A

Monitoring

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15
Q

What is the treatment of in-situ ductal breast carcinoma?

A

Lumpectomy + Radiation
Mastectomy

Hormone receptor (+)? = consider endocrine therapy

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16
Q

What are some surgical options for invasive breast cancers?

A

Lumpectomy + radiation
Mastectomy +/- radiation
& chemo/target/endocrine therapy

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17
Q

Why do we use chemotherapy even after mastectomy or lumpectomy?

A

Systemic chemo can destroy any lingering cancer cells to prevent relapse (mop up)

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18
Q

What are the two paths for invasive breast cancer treatment? What if they are Hormone (+)? Hormone (-)?

A

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!

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19
Q

What SIZE should a breast cancer tumor be to qualify for chemotherapy?

A

Since chemo is toxic, limit!
>1 cm = give chemo
0.6 - 1 cm = consider chemo
≤0.5 cm = AVOID

20
Q

What is the Oncotype DX tool?

A

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

21
Q

What chemo do we use for ER/PR (+/-) & HER2(-) breast cancer?

A

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

22
Q

What chemo do we use SPECIFICALLY for ER/PR (-) & HER2(-) breast cancer?

A

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

23
Q

What chemo do we use for HER2(+) breast cancer?

A

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

24
Q

What drugs are HER2-specific and downregulate HER2 expression?

A

Trastuzumab, Pertuzumab

25
Q

What is a major AE with docetaxel? How can we prevent this?

A

Peripheral edema
- premeditate with dexamethasone

26
Q

What are key counseling points for doxorubicin?

A

Cardiotoxicity (recall)
RED urine/secretion discoloration
Increased secondary malignancies
Blistering, extraspatial leakage

27
Q

What are some key counseling points for cyclophosphamide?

A

Hemorhagic cystitis (significant bladder irritation)
Sterility

28
Q

What are some key counseling points for trastuzumab/pertuzumab?

A

Cardiotoxicity [CHF, ventricular dysfunction]
- reversible
Diarrhea (pertuzumab)
Infusion rxns

29
Q

How does the location of estrogen production vary between pre and post menopausal women?

A

Pre-menopause = ovaries
Post-menopause = via aromatase (concentrated in peripheral adipose tissue)

30
Q

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?

A

Tamoxifen - prodrug of hepatically active endoxifen
AVOID strong CYP2D6 inhibitors required for prodrug conversion!
Ie. fluoxetine, paroxetine, bupropion
Citalopram, escitalopram, venlafaxine, mirtazipine are permitted

31
Q

What adjuvant endocrine therapy should PRE-MENOPAUSAL women use for breast cancer?

A
  1. Tamoxifen
  2. Aromatase inhibitor + ovarian suppression (simulates post-menopause)
32
Q

What adjuvant endocrine therapy should POST-MENOPAUSAL women use for breast cancer?

A
  1. Aromatase inhibitor
  2. Consider Tamoxifen
33
Q

How is ovarian suppression achieved?

A

Oophorectomy
LHRH agonists (recall from prostate cancer)
- Goserelin 3.6 mg SQ month
- Leuprolide 3.75 mg IM q28 days

34
Q

What are important counseling points about risks with tamoxifen in breast cancer treatment? What are some AEs?

A

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)

35
Q

What are important counseling points about risks with aromatase inhibitors in breast cancer treatment? What are some AEs?

A

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

36
Q

What are some of the aromatase inhibitors we use in endocrine therapy?

A

Anatrazole
Letrozole
Exemestane

37
Q

What are some additional adjuvant therapies for breast cancer patients who have tried chemo/surgical/endocrine therapies?

A

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

38
Q

What treatments should be used in METASTATIC, ER/PR(+) HER2(-) breast cancer?

A

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

39
Q

When a patient has METASTATIC breast cancer, when should chemo be initiated?

A

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

40
Q

What kinds of metastatic breast cancer patients would qualify for combination chemotherapy?

A

Very high performance status, at an early stage of treatment for rapid control

41
Q

What is first line treatment for METASTATIC, HER2(+) breast cancer? What are other options if this doesn’t work?

A

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

42
Q

What are THREE Ab-Drug conjugates we may use in metastatic breast cancer?

A

Fam-trastuzumab deruxtecan-nxki
Ado-trastuzumab emtansine
Sacituzumab govitecan-hziy

43
Q

What two agents may be considered in patients with bone metastases from metastatic breast cancer?

A

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

44
Q

What are some tumor markers to recognize in breast cancer? (3)

A

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]

45
Q

What are some important survivorship issues to consider in breast cancer patients? (Aka QoL)

A

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

Crit Care, Oncology & Hematology (18 decks)

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