Lecture 9: Breast Cancer

Breast Cancer may be from specific genetic mutation:

-familial breast cancer

-___ mutation (tumor suppressor gene)

-____ and ____ mutations

p53, BRCA 1, BRCA 2

Breast Cancer Risk Factors

1. female

2. older ___

3. ___ mutations

4. family history of breast cancer (__ and __ degree relatives, __ onset of breast cancer in a family member)

age, genetic, first, second, early

Breast Cancer Risk Factors

5. endogenous estrogen exposure:

___ menarche (≤14 years old)

___ menopause (≥55 years old)

___ age at birth of first child (>30 years old)

early, late, older

Breast Cancer Risk Factors

6. benign breast tissue

7. ___ exposure

8. ____/high BMI

9. low physical activity

10. alcohol ingestion

radiation, obesity

Breast Cancer Risk Factors-Controversial

11. exogenous estrogen exposure:

___ ___ (benefits usually outweigh risks)

____ ____ ___ (inconsistent data)

oral contraceptives, estrogen replacement therapy

Factors associated with lower risk:

1. _____

2. moderate or vigorous ____ activity

3. maintaining a healthy body ___

breastfeeding, physical, weight

Prevention

-prophylactic ____

-bilateral _____ (removal of ovaries)

-drug therapy prevention with ____ and ____ for women at high risk

masectomies, oophorectomies, tamoxifen, raloxifene

Screening

-breast ___ examination (BSE)

-____ breast examination (CBE)

-gold standard = _____!

self, clinical, mammography

Screening Recommendations

-no concensus among organizations

-around ___ birthday, patients should have conversation with doctor about having mammogram

40th

Signs and Symptoms

-many patients are ____

-80% of women detect some abnormality themselves

-may be ___ ____ in or near the breast or underarm area

-may be stabbing or aching __

-less common symptoms are nipple tenderness, change in size/shape of breast, erythema, scaling, eczema, swelling, peau d'orange

asymptomatic, painless lump, pain

Site of Metastases

-____

-____

-____

-brain

-skin

bone, liver, lung

Diagnosis

-history and physical examination

-diagnostic mammography (may also undergo ultrasound)

-___ of mass

-other imaging studies (CT scan, bone scan)

biopsy

Pathologic Types

1. ___ carcinoma in situ (DCIS) - premalignant lesion

2. ___ carcinoma in situ (LCIS) - not a premalignant lesion, both breasts at equal risk

ductal, lobular

Pathologic Types

3. ___ ___ ___- most common type, worst prognosis

invasive ductal carcinoma

From initial biopsy, can identify hormone receptor status by looking at ___ and/or ___ receptors

estrogen, progesterone

Hormone receptor status

-____ and/or ___ tumors are generally less aggressive than negative ones

ER+, PR+

Hormone receptor status

-if ER+ or PR+, can use ___ ____ to prevent recurrence after treatment is completed

endocrine therapy

biopsy will also tell us if ___ is overexpressed or amplified

Her2neu

Her2neu Overexpression/Amplification

-generally associated with ___ prognosis, more aggressive disease, ___ to chemotherapy

-testing is used to select which patients will benefit from __-__ therapy

poorer, resistant, anti-Her2neu

Early Stage = ___, ___, ___

I, IIA, IIB

Early Stage (Stage I and II) Treatment

-goal of tx = ___!

-____ ___ is standard

cure, surgical resection

Early Stage (Stage I and II) Treatment

-surgical resection is standard. Either remove entire breast with modified radical ____ OR remove part of breast with breast conserving surgery (____)

masectomy, lumpectomy

Patients who get breast conserving surgery (lumpectomy) MUST be willing to undergo ___

XRT (radiation)

Patients who get modified radical masectomy MIGHT need XRT--only if cancer has traveled to ___ ___

lymph nodes

Early Stage (Stage I and II) Treatment

-consider ___ chemotherapy for tumors that are too large for ____

neoadjuvant, lumpectomy

Early Stage (Stage I and II) Treatment

-after surgery, we might irradicate _____ disease with ___ chemotherapy or ___ therapy

micrometastatic, adjuvant, biologic

Which Early Stage Patients MUST have Adjuvant Chemo?

ER and PR _____

or

Her2neu ____

or

cancer present in ___ __

negative, positive, lymph nodes

If patient is ER+ or PR+, Her2neu negative, and negative for cancer in lymph nodes (best case scenario), we can do more specific testing on tumor to determine benefit of ___ ___

adjuvant chemotherapy

more specific testing on tumor includes ____ ____ to help determine likelihood of recurrence and benefit of adjuvant chemotherapy

oncotype diagnosis

3 workhorse drugs in breast cancer

A = ____ (eg doxorubicin, daunorubicin)

C = ___ ____ (eg cyclophosphomide, carboplatin)

T = ____ (eg paclitaxel, docetaxel)

anthracyclines, alkylating agents, taxanes

What is standard of care adjuvant chemo regimen for Early Stage patients?

AC→T

What is another adjuvant chemo regimen for Early Stage patients that is kinder/gentler because there is no anthracycline agent?

TC

What is another adjuvant chemo regimen for Early Stage patients that is the most aggressive?

TAC

If Early Stage patient needs radiation, we do it ___ adjuvant chemo is completed to prevent risk of infection

after

If cancer is Her2neu positive, patient must also get:

H = ____

trastuzumab (herceptin)

Trastuzumab (Herceptin)

-major ADR = ____

cardiac (CHF, MI, decreased LVEF)

DO NOT administer Trastuzumab concurrently with an ___ (eg -rubicin drug); anthracycline causes ___, monitor ___ every __ months

anthracycline, HF, ECHO, 3

What are the 2 preferred trastuzumab-containing adjuvant chemotherapy regimens?

AC→TH, TCH

HER2 negative + need chemo —> __ options

HER2 positive + need chemo —> __ options (Trastuzumab)

3, 2

Endocrine therapy

-recommended in ___ or __ tumors regardless of menopausal status, age, or HER2 status of tumor

-prevents ____

ER+, PR+, recurrence

Endocrine therapy

-chemotherapy should be given ___, then endocrine therapy (bc prevents cancer from coming back)

first

Endocrine Therapy Options:

1. ____

2. ___ ___

tamoxifen, aromatase inhibitors

Tamoxifen

-most firmly established adjuvant endocrine therapy, works well

-selective estrogen receptor modulator (SERM)

-___ with estradiol binding to estrogen receptors

competes

Tamoxifen ADRs

-___ ___

-vaginal dryness/discharge

-irregular ____

-endometrial thickening

hot flashes, menses

Tamoxifen ADRs-Serious

-____

-endometrial/uterine ___

thromboembolism, cancer

Tamoxifen

-20mg ALL ___ DAILY with ___

-Avoid ____ and ____, because these drugs decrease tamoxifen's effects

PO, food, fluoxetine, paroxetine

Tamoxifen Possible Benefits

-may prevent __ loss

-lowers total ___

bone, cholesterol

Aromatase Inhibitors

-inhibits aromatase (enzyme that catalyzes conversion of androgens to estrogens)

-no intrinsic __ properties

-no _____ ____ since no estrogen being made

hormonal, menopausal symptoms

Aromatase Inhibitors

1. ____ (Arimidex) (non-steroidal)

2. ____ (Femara) (non-steroidal)

3. ___ (Aromasin) (steroidal)

anastrazole, letrozole, exemestane

Aromatase Inhibitors ADRs

-_____/increased rate of ___ ___

-musculoskeletal pain, arthralgias

osteoporosis, bone fractures

When patient is premenopausal, ovaries are making estrogen, so must give ___

tamoxifen (5-10 years)

When patient is postmenopausal, fat tissues are making estrogen, so must give ___ ___

aromatase inhibitors (5-10 years)

Should we surgically or chemically force a premenopausal into menopause?

no