- mammogram features concerning for malignancy - feature suggesting benignity

- spiculated soft tissue mass (most specific) - microcalcifications - irregularly outlined more common than rounded - solid mass suggests benign

- 21-gene assay that provides a numerical score to quantify risk of recurrence for ER positive breast cancer - also predictive of adjuvant chemotherapy benefit

Breast cancer Flashcards by Ned Jones

Indication for obtaining oncotype score

Assesses 16 cancer-related genes and 5 normal comparator reference genes, and is therefore sometimes known as the 21-gene assay.
**It was designed for use in estrogen receptor (ER) positive tumors. The test is run on formalin fixed, paraffin-embedded tissue. Oncotype results are reported as a Recurrence Score (RS), where a higher RS is associated with a worse prognosis, referring to the likelihood of recurrence without treatment. In addition to that prognostic role, a higher RS is also associated with a higher probability of response to chemotherapy, which is termed a positive predictive factor.

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interpretation of oncotype score

For women older than 50 years of age:

Recurrence Score of 0-25: The cancer has a low risk of recurrence. The benefits of chemotherapy likely will not outweigh the risks of side effects.
Recurrence Score of 26-100: The cancer has a high risk of recurrence. The benefits of chemotherapy are likely to be greater than the risks of side effects.
For women age 50 and younger:

Recurrence Score of 0-15: The cancer has a low risk of recurrence. The benefits of chemotherapy likely will not outweigh the risks of side effects.
Recurrence Score of 16-20: The cancer has a low to medium risk of recurrence. The benefits of chemotherapy likely will not outweigh the risks of side effects.
Recurrence Score of 21-25: The cancer has a medium risk of recurrence. The benefits of chemotherapy are likely to be great than the risks of side effects.
Recurrence Score of 26-100: The cancer has a high risk of recurrence. The benefits of chemotherapy are likely to be greater than the risks of side effects.

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anthracyclines

*All the -rubicins

Doxorubicin, epirubicin, idarubicin, daunorubicin, Pegylated liposomal doxorubicin

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Perjeta generic name

pertuzumab

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high risk features of early stage breast cancer

high-grade tumor, large tumor size (≥2 cm), pathologically involved lymph nodes, and/or high 21-gene recurrence score

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what is atypical ductal hyperplasia (ADH)?

Precursor to DCIS

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duration of adjuvant endocrine therapy

Given node+ (>3), continue ET for 10 years (ATLAS – DFS + OS benefit)
Given 1-3 (CONFIRM), Determine Breast cancer index (BCI) to predict risk
Given node negative (<3)
high risk of recurrence (based on breast cancer index) → continue ET for 10 years (ATLAS)
low risk of recurrence → continuation for 5 years is individualized

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Highest risk race for breast cancer

Higher risk among white females

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Histologic subtypes of in situ breast cancer

Ductal

Lobular

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most favorable histologic subtypes

Tubular and mucinous

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Define the histologic subtypes of breast cancer

Invasive ductal carcinoma
lobular
mixed
mucinous
tubular
medullary
metaplastic
papillary
cribriform

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most common histologic subtypes

infiltrating ductal (75%)
infiltrating lobular (5-10%)

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Receptor phenotype of lobular carcinoma

vast majority are ER positive + display loss of E-cadherin

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Role for clinician and self breast exams

Some organizations recommend clinical breast exam yearly after age 40. Breast SELF-exam not recommended.

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mammogram features concerning for malignancy

- feature suggesting benignity

spiculated soft tissue mass (most specific)
microcalcifications
irregularly outlined more common than rounded
solid mass suggests benign

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Clinical utility of US

distinguishing between cystic and solid masses

- further information on likely of a solid mass being malignant

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Test characteristics + clinical utility of MRI for assessment of breast cancer

Most sensitive modality but low specificity (benign breast lesions also enhance), but improvement in specificity hasn’t shown survival benefit in preoperative planning

Complement to mammogram for dense breasts
for invasive cancers contiguous to the chest wall, MRI may be needed for surgical planning.

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effect of ER and PR status on breast cancer prognosis

ER/PR-negative tumors have a worse prognosis

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what is oncotype DX?

21-gene assay that provides a numerical score to quantify risk of recurrence for ER positive breast cancer
also predictive of adjuvant chemotherapy benefit

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Management of lobular carcinoma in situ (LCIS)

Primary surgery, followed by risk reduction – (tamoxifen, raloxifine, aromatase inhibitors, bilateral prophylactic mastectomy)

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Risk of future invasive breast cancer in a patient with LCIS?

1% per year

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Management of DCIS

Mastectomy with SLNB OR lumpectomy with XRT

- tamoxifen if ER positive, unless undergoing bilateral mastectomy

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Survival benefit of mastectomy versus lumpectomy

None

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Initial treatment options for operable, early stage breast cancer?

1) Lumpectomy with surgical staging of the axillary lymph nodes
2) Total mastectomy with surgical staging of the lymph nodes
3) Neoadjuvant chemotherapy to permit breast conserving therapy

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Next step for BiRads 0

Additional evaluation is required for further characterization, which may include additional mammographic views and or ultrasound and, rarely, magnetic resonance imaging (MRI).

why microcalcifications suggest breast cancer

They are intraductal calcifications in areas of necrotic tumor

management of brca 1 and 2 carrier and age

BRCA1 carrier: Bilateral salpingo-oophorectomy by age 35-40 after childbearing (earlier in BRCA1) + Prophylactic bilateral mastectomies BRCA2 carrier: Bilateral salpingo-oophorectomy by age 40-45 Prophylactic bilateral mastectomies

what is the function of aromatase?

converts circulating androgens to estrogen

Name some of the common non-trastuzumab-based regimens for neoadjuvant and adjuvant treatment of breast cancer

ACT (docetaxel, doxorubicin, cyclophosphamide) (taxane-AC) Dose-dense AC TC (docetaxel/cyclophosphamide)

what is is AC regimen?

doxorubicin/cyclophosphamide

Firstline systemic therapy for HER2-positive metastatic disease

trastuzumab + pertuzumab + taxane until maximum tumor response, followed by maintenance trastuzumab + pertuzumab

Palbociclib indication

ER/PR+ metastatic breast cancer in postmenopausal women

indication for lapatinib

Second line for HER2-positive breast cancer (confirm)

Management of fibroadenoma

- Primary surgery - path to rule out phyllodes tumor

What is a phyllodes tumor

Large, fast-growing masses that form from the periductal stromal cells of the breast.

Upper limit of breast cancer screening per ASCO and underling point

Life expectancy of 10 or more years. It should really be individualized based on someone's health status, not some arbitrary cutoff.

Stage at which most patients present

Vast majority present without metastatic disease

Locally advanced includes which stages?

IIIA-IIIC | Subset of patients with IIb

Early stage breast cancer includes

Stage I, IIA, or subset of IIb

Management of early stage breast cancer

Primary surgery and surgical axillary staging with or without RT Adjuvant chemo depending on tumor size, grade, number of involved lymph nodes, ER/PR status, HER2 However — triple negative typically treated with neoadjuvant chemo

Criteria precluding BCT

Multi centric disease Large tumor size in relation to breast *Diffuse malignant calcification on imaging *Prior chest RT Persistently positive margins despite attempts at re-excision

Initial workup (in addition to imaging)

1) Bilateral mammogram 2) US 3) Determination of ER/PR status and HER2 4) Genetic counseling if at risk for hereditary breast cancer syndrome 5) Pregnancy counseling 6) Imaging based on symptoms PET/CT if stage IIIA or higher

Management of early stage patient with suspicious axillary lymph nodes

US + FNA or core biopsy

Management of patient with early stage BC and positive biopsy of axillary nodes

If going directly to surgery — axillary node dissection

Management of patient with early stage BC and negative biopsy of axillary nodes

Sentinel lymph node biopsy at time of surgery

Management of early stage patient with negative axillary examination

SLNB at time of surgery

Role for HER2-directed therapy in early stage

Used if tumor is greater than 1 cm, in combination with chemo. Use for small cancers is controversial.

Adjuvant management of triple negative early stage breast cancer AND indication

Adjuvant chemo if tumor greater than 0.5 cm

Goal of systemic therapy for locally advanced BC

Induce a tumor response and enable BCT

Management of patient progressing on neoadjuvant systemic therapy

Proceed directly to surgery rather than switching regimen

Management of patient who has complete clinical and/or radiographic response to NAC

Proceed to surgery still

Role for adjuvant therapy in locally advanced

— HER2 positive following completion of surgery to complete a year of treatment — continue endocrine therapy

Breast cancer surveillance

Annual diagnostic mammo for 3-5 years then switch to screening mammo

Prognostic significance of intramammary lymph nodes

Worse prognosis

Mammogram laterality in surveillance

IF mastectomy --> no need IF BCT --> still need Always need bilateral otherwise (women with BC in one breast are at higher risk of breast cancer in other breast)

Risk factors for breast cancer

- Age - White - Dense breast tissue - Obesity - Hormone therapy - Smoking (modest) - RT (hodgkins patients) - Increased age at first full-term pregnancy

Role for clinical breast exam

As part of physical exam in surveillance period

Options for risk reduction following surgery for LCIS

tamoxifen, raloxifine, aromatase inhibitors, bilateral prophylactic mastectomy

adriamycin generic name

doxorubicin

Palbociclib mechanism

CDK4/6 inhibitor

lapatinib mechanism

Small molecule inhibitor of VEGF + HER2

Generally what differentiates early stage from locally advanced

presence of axillary adenopathy

Common mechanism of resistance to anti-estrogen therapy

activation of the mTOR signaling pathway

Phenotype of most BRCA1 breast cancers

triple negative

Phenotype of most BRCA2 breast cancers

ER+

Additional cancer types associated with BRCA2

- ovarian, gastric, melanoma, prostate, pancreatic

Additional cancer types associated with BRCA1

- ovarian

SRE reduction in anyone on an aromatase inhibitor

Zometa for up to 2 years

When to start screening women for breast cancer who've had chest wall radiation (eg for hodgkins)

- 10 years after XRT OR at age 40, whichever comes first

Management of localized tubular carcinoma of the breast

Partial mastectomy with axillary sentinel lymph node biopsy

tubular carcinoma of the breast clinical behavior

Excellent outcomes, do well

First line for postmenopausal woman with ER, PR + breast cancer

CDK4,6 inhibitor + AI (letrozole)

First line neoadjuvant for locally advanced triple negative breast cancer?

carbo/taxol + pembrolizumab, followed by doxorubicin/cyclophosphamide

Management of residual disease after neoadjuvant therapy in locally advanced breast cancer

Capecitabine

adjuvant therapy in early stage for HER2+, ER+

taxol-trastuzumab followed by aromatase inhibitor

Firstline for triple negative MBC

Chemoimmunotherapy Pembro if CPS greater than 10

First line for triple negative MBC + chemo options

Single agent chemo(taxol vs. abraxane vs. gem/carbo) +\- IO if PD-L1 CPS greater than 10%

First line for HER2 positive MBC

Trastuzumab + pertuzumab + taxane

Imaging modality + frequency needed for hodgkin's patients treated with chest wall radiation

annual mammogram + MRI

Second line for HER2 + metastatic

Trastuzumab deruxtecan (T-DXd) (newer ADC w/ higher payload + bystander effect) (DESTINY-Breast03)

Adjuvant therapy for male breast cancer

Tamoxifen (can't use AI due to concerns it may lead to incomplete estradiol suppression)

What is TCHP?

Docetaxel (Taxotere) Carboplatin (Paraplatin) Trastuzumab (Herceptin) Pertuzumab (Perjeta)

Indications for neoadjuvant chemotherapy with HER2+ disease

Node positive or large tumors (greater than 2 cm)

Management of HER2 positive breast cancer with pathCR

continue trastuzumab with pertuzumab (Dual HER2 blockade) for total 1 year

Management of HER2 positive with incomplete response to NAC

adjuvant ado-trastuzumab emtansine (T-DM1) for 14 cycles, rather than trastuzumab (KATHERINE)

when raloxifene is indicated

postmenopausal

Indications for neoadjuvant for triple negative

T2 or T1N+ (CONFIRM)

Additional RF

OCP's (patients at increased risk, with family members with BC) should consider stopping oral contraceptives

Intervention with survival benefit in BRCA patients

BSO bilateral mastectomy has NOT been shown to have a survival benefit

Drug indicated for PIK3CA + for what receptor status

- alpelisib - hormone receptor positive

Role for PIKC3A therapy in breast

Second line for metastatic hormone receptor positive

Indication for bisphosphonate in breast cancer

IF adjuvant therapy planned AND postmenopausal REGARDLESS of receptor phenotype

Sequencing of adjuvant XRT, endocrine, and chemotherapy for adjuvant hormone positive

Adjuvant chemotherapy, radiation therapy, followed by adjuvant endocrine therapy

Nodal involvement warranting adjuvant radiation therapy

More than 3

T-Dxd payload mechanism of action

Topoisomerase inhibitor

NAC for HER2 positive and why

Trastuzumab/pertuzumab + nonanthracycline based chemo (TCHP) - study showed nonanthracyclne based regimen had similar OS, so TCHP is less toxic with comparable outcomes

what is considered locally advanced disease

*T3 or greater, N2 or N3 disease

Adjuvant therapy for early stage node negative HER2+ breast cancer

Taxol + trastuzumab (de-escalation appropriate)

Management of breast cancer in patient with Li fraumeni syndrome

mastectomy rather than lumpectomy with radiation (high risk of recurrent cancer so no radiation)

BiRADS 2 management

Repeat mammogram every 6-12 months for 2-3 years to document stability IF enlarging, biopsy

BI-RADS 2 management

Continue regular screening

Evidence for PARP inhibitors for BRCA mutant patients with metastatic disease

PFS but no OS benefit so not recommended (Confirm)

Risk of developing contralateral breast cancer in BRCA2 mutant patient with breast cancer over 20 years AND risk of developing ovarian cancer

25% - ovarian cancer - 15-20%

Which BRCA mutation is higher risk for ovarian cancer? What is the risk over 20 years?

BRCA1 (40-45%)

NAC regimen for PD-L1 positive triple negative

carbo/taxol + pembrolizumab, followed by doxorubicin/cyclophosphamide

Adjuvant endocrine therapy in premenopausal woman

ovarian suppression + aromatase inhibitor

Surveillance modality for patients who've had chest wall radiation

annual breast MRI (after age 25 years) and annual screening mammogram (after age 30 years). MRI and mammogram are often alternated every six months.

Systemic therapies contraindicated in pregnancy

- HER2-directed therapy - antiestrogen therapy *you can use anthracyclines and cytoxan during second trimester

When is axillary lymph node dissection required after surgery in breast?

Greater than 3 lymph nodes involved on sentinel lymph node biopsy