Breast Cancer

breast cancer

What is the most common type of cancer in women?

2nd

Breast cancer is the ________ leading cause of cancer related deaths in women.

risk factors for breast cancer

• Age

• Female Sex

• Endocrine

• Genetic

• Environmental and Lifestyle

- Alcohol consumption

- Tobacco Use

- Radiation exposure

- High BMI

endocrine risk factors

• Early menarche (period): < 11 y/o

• Late menopause: ≥ 55 y/o

• Late age of first birth: ≥30 y/o

• Nulliparity (no children)

• HRT: estrogen + progestin

genetic risk factors for breast cancer

Personal history may ↑ risk

- Ovarian/endometrial cancer

- Hyperplasia of breast

- Dense breast tissue

• Family history may ↑ risk

- In the U.S. ~10% breast cancers related to family history

- Women's risk ↑ by ~50% if have 1st degree relative with breast cancer

• Risk is ↑ if women + relative are <50 y/o at diagnosis

- There is risk if have 2nd degree relative with breast cancer

• Genes associated:

- BRCA1 & BRCA2

- TP53, CHEK2, PALB2, PTEN, ATM

• BRCA1 & BRCA2:

- Tumor suppressor genes → DNA repair

- Mutation increases risk of breast cancer to 70%

• 1/400 people with clinically significant mutations in U.S

monthly

For a pt with average risk for breast cancer, they should do a self breast exam at the age of > or = 25 __________

1-3 yrs

If a pt is average risk for breast cancer and aged 25-39 how often should they get a clinical breast exam?

annually

If a pt is average risk for breast cancer and > or = 40 yo how often should they get a clinical breast exam?

annually

If a pt is average risk for breast cancer and > or = 40 yo how often should they get a mammography?

monthly

High risk pts for breast cancer > or = 25 yo should do _________ self breast exams

every 6-12 mo

How often should high risk pts for breast cancer age > or = 21 have a clinical breast exam?

25

In high risk pts for breast cancer the timing for a mammography is dependent on the risk factor but you should not begin prior to the age of ________

high risk

lifetime risk ≥20%, thoracic radiation between ages 10-30, 5-year risk ofinvasive cancer ≥ 1.7% (Gail Model), known genetic mutation, dense breast tissue

painless

The usual initial presentation of breast cancer is a _________

typical characteristics of cancerous lump

- Solid/hard

- Irregular

- Nonmobile

- Unilateral

less common characteristics of cancerous lump

- Dimpling

- Retraction

- Nipple discharge

- Pain

- Skin changes

-Bone

-Liver

-Brain

-Lungs

-Skin

What are the common locations of breast cancer metastases?

s/s of metastases

-jaundice

-abdominal pain/distention

-dyspnea

-altered mental status

-bone pain

-mammography

-ultrasound

-MRI of breast

(if abnormal -> biopsy)

What is used to dx breast cancer?

biopsy

- Evaluation of pathology

- Identification of receptor status and genetic mutations

invasive carcinoma

• Ductal vs. lobular

• ~75% of invasive breast cancers = invasive/infiltrating ductal carcinoma

noninvasive carcinoma (in situ)

• Ductal vs. lobular

• DCIS more common than LCIS

• *often diagnosed as result of mammogram screening

ductal carcinoma in situ

DCIS

lobular carcinoma in situ

LCIS

receptor status

-imp to look at for prognostic/predictive factors

-tx varies based on receptor status

estrogen receptor

ER

progesterone receptor

PR

human epidermal growth factor receptor 2

HER2

symptomatic

You only look for metastatic disease in breast cancer if the pt is:

diagnostic tests (if symptomatic)

-chest/abdominal CT

-brain MRI

-bone scan

-PET scan

CT

looks for abnormal structures but doesnt tell you the function

PET

actually tells you the function so it is common in all cancers except colon

surgery

mainstay for tx of all stages of breast cancer except metastatic (goal is to not remove that many lymph nodes)

stage I and II

early breast cancer

stage III

locally advanced breast cancer

stage IV

advanced or metastatic breast cancer

locoregional therapy

-surgery

-radiation

breast conserving therapy and mastectomy

What are the 2 types of surgeries?

breast conserving therapy (BCT)

removal of part of breast and surgical evaluation of axillary lymph node basin (lumpectomy, partial mastectomy)

mastectomy

-recommended by NCCN when BRCA1 or BRCA2 mutation present

-recurrence risk is low and no radiation

-all lymph nodes = gone (bad)

-reconstructive surgery?

radiation

after breast conserving therapy reduces 10 yr risk of recurrence by 16% and 15 yr risk recurrence by 4%

systemic therapy

-chemo

-targeted therapy

-endocrine therapy

Neoadjuvant (Pre-Operative)

Therapy prior to surgery

- ↓ size of tumor → could minimize extent of surgery

- Determine response to treatment

adjuvant

-Therapy after surgery/radiation

-This phase is important due to prevent disease recurrence

(eliminates micro metastatic disease)

higher chance of it coming back

Why is radiation required after breast conserving therapy surgery?

surgery!!

pt decides which one they would rather do (benefit/risk)

What is the 1st step in tx of noninvasive/in situ (stage 0) breast cancer?

nothing

Once stage 0 pt has surgery, you check for HR status. If the pt is HR- what do you do?

endocrine therapy for 5 yrs

Once stage 0 pt has surgery, you check for HR status. If the pt is HR+ what do you do?

cure

What is the goal of tx in stage 0 breast cancer?

surgery (pt chooses which one)

What is the first step in stage I and II breast cancer (invasive early stage)?

oncotype score/lymph node involvement determines adjuvant chemo

If a pt is stage I or II (invasive early stage) and HR+; HER2- what do you do to decide if they need systemic therapy?

adjuvant chemo + HER2 directed tx

If a pt is stage I or II (invasive early stage) HR+; HER2+ what do you do?

adjuvant chemo + HER2 directed tx

If a pt is stage I or II (invasive early stage) HR-; HER2+ what do you do?

adjuvant chemo if T> 1 cm or N+

If a pt is stage I or II (invasive early stage) HR-; HER2- what do you do?

endocrine tx

Once a pt with stage I or II (invasive early stage) does adjuvant chemo and or radiation, you get their histology back as HR+; HER2- what do you do?

-HER2 directed tx

-endocrine tx

Once a pt with stage I or II (invasive early stage) does adjuvant chemo and or radiation, you get their histology back as HR+; HER2+ what do you do?

HER2 directed tx

Once a pt with stage I or II (invasive early stage) does adjuvant chemo/ and or radiation, you get their histology back as HR-; HER2- what do you do?

Olaparib if BRCA mutation pos

Once a pt with stage I or II (invasive early stage) does adjuvant chemo, you get their histology back as HR-; HER2- what do you do?

cure

What is the goal of tx in stage I and II (invasive early stage)?

genetic testing for adjuvant tx

-used to identify those at risk of developing metastasis in node-neg pts

-oncotype Dx

Oncotype Dx

- Screens for expression of 21 genes

- Reports recurrence score that correlates with risk of distant recurrence or death from breast cancer in pts with ER/PR+, node negative invasive disease

give chemo

If a pt has a Oncotype Dx score of > or = 26 you should:

• Inoperable breast cancer due to size (too lrg)

• HER2+ or TNBC (triple neg)

• Surgery may be delayed

Who gets neoadjuvant systemic therapy in stage II-III (locally advanced invasive) breast cancer?

everyone (pt picks which one)

Who gets surgery in stage II and III (locally advanced invasive) breast cancer?

• Endocrine tx

• BRCA mutation- olaparib

• High Risk- abemaciclib, ribociclib

If a pt with stage II-III (locally advanced invasive) breast cancer is HR+; HER2- after surgery what do you do?

• HER2 directed therapy

• Endocrine tx

If a pt with stage II-III (locally advanced invasive) breast cancer is HR+; HER2+ after surgery what do you do?

HER2 directed therapy

If a pt with stage II-III (locally advanced invasive) breast cancer is HR-; HER2+ after surgery what do you do?

• Pembrolizumab (if used neoadjuvant)

• BRCA mutation- olaparib

• Capecitabine (residual disease)

If a pt with stage II-III (locally advanced invasive) breast cancer is HR-; HER2- (triple neg) after surgery what do you do?

-ddAC and paclitaxel

OR

-TC

HR+; HER2- neoadjuvant/adjuvant preferred regimens

Doxorubicin + Cyclophosphamide

ddAC

Docetaxel + Cyclophosphamide

TC

Olaparib

In the adjuvant setting with HR+, HER2- with the BRCA mutation what do you give?

• Abemaciclib for 2 years OR

• Ribociclib for 3 years

If a pt is high risk HR+, HER2- what do you add in addition to endoccrine therapy?

ddAC + paclitaxel: (Doxorubicin + Cyclophosphamide + Paclitaxel)

OR

TC (Docetaxel + Cyclophosphamide)

What is the HR-, HER2- neoadjuvant/adjuvant preffered regimens in stage I?

High risk TNBC

• Neoadjuvant pembrolizumab+ carboplatin+ paclitaxel followed by pembrolizumab + cyclophosphamide + doxorubicin followed by adjuvant pembrolizumab

If a pt is HR-, HER2- stage II-III what is the preferred neoadjuvant/adjuvant?

capecitabine -> use instead of adjuvant keytruda

If a pt is HR-/HER2- with residual disease after neoadjuvant tx what do you do?

olaparib

used in adjuvant setting in BRCA mutation in HR-, HER2-

Enhurtu + THP

• Fam-trastuzumab deruxtecan (4 cycles) then paclitaxel + trastuzumab + pertuzumab (4 cycles)

HER2+ preferred regimen for neoadjuvant use only:

TCH

• Docetaxel + Carboplatin (6 cycles) + Trastuzumab*

HER2+ preferred regimen for adjuvant only:

TCHP

• Docetaxel + Carboplatin (6 cycles) + Trastuzumab* + Pertuzumab*

HER2+ preferred neoadjuvant or adjuvant:

• Ado-trastuzumab (Kadcyla)

• Fam-trastuzumab deruxtecan (Enhurtu)

If residual disease occurs after preoperative tx in HER2+ what do you do?

increased risk of HFrEF

Why do we not use doxorubicin in HER2+ pts?

tamoxifen

if using ovarian suppression/ablation -> AI

Preferred Endocrine Regimens for ER/PR+ Premenopausal:

AI preferred

Preferred Endocrine Regimens for ER/PR+ postmenopausal:

5 yrs (can be up to 10 depends on lymph node involement)

What is the min amount of time you treat HR+ pts?

stage IV (metastatic disease) dx

- Lab/Imaging recommendations based on patient's symptoms

- Obtain new biopsy for gene testing

• Used to identify potential use of targeted agents

- Systemic treatment indicated

- Limited use for surgery/radiation outside of palliative treatment

Tx for stage IV (metastatic disease):

Inavolisib (Itovebi)+ Alpelisib (Piqray)

If a pt has stage IV (metastatic stage) with PIK3CA mutation what do you give?

Capivasertib (Truqap)

If a pt has stage IV (metastatic stage) with PIK3CA, AKT1 or PTEN mutation what do you give?

Elacestrant (Orserdu), Imlunestrant (Inluriyo), Vepegestrant (Veppanu)

If a pt has stage IV (metastatic stage) with ESR1 mutation what do you give?

Olaparib (Lynparza), Talzoparib (Talzenna)

If a pt has stage IV (metastatic stage) with BRCA mutation what do you give?

CDK4/6 inh + AI or fulvestrant

If a stage IV (metastatic) has no targeted mutation present with HR+, HER2- what do you give?

Chemo or endocrine + HER2 directed therapy

If a stage IV (metastatic) has no targeted mutation present with HR+, HER2+ what do you give?

Chemo + HER2 directed therapy

If a stage IV (metastatic) has no targeted mutation present with HR-, HER2+ what do you give?

-Chemo

-If PD-L1>10, add pembrolizumab

-If BRCA1/2 mutation: PARP inhibitor

If a stage IV (metastatic) has no targeted mutation present with HR-, HER2- what do you give?

palliative, prevent progression, prolong life expectancy

What is the goal of tx in stage IV (metastatic) breast cancer?

Add denosumab, zoledronic acid, or pamidronate

If a pt with stage IV (metastatic) has bone metastasis present then you need to add:

Anthracyclines (Topoisomerase II):

• Doxorubicin

• Liposomal doxorubicin

Antimicrotubular (Taxanes):

• Paclitaxel

Antimetabolites:

• Capecitabine

• Gemcitabine

Microtubule inhibitors:

• Vinorelbine

• Eribulin

NCCN Preferred Regimens for HER2- Metastatic Disease:

• Pertuzumab + Trastuzumab + Docetaxel

OR

• Pertuzumab + Trastuzumab + Paclitaxel

OR

• Fam-trastuzumab deruxtecan + Pertuzumab

NCCN Preferred Regimens for HER2+ Metastatic Disease

Anthracycline (Topoisomerase II Inhibitor)

Doxorubicin class: