Oncology: Breast Cancer

Options to start screening with mammogram every year

Women between 40-44 yo

Should get mammograms every year

Women 45-54 yo

Mammogram every other year or yearly as long as life expectancy is greater than 10 years

Women 55 and older

Clinical breast exams

Not recommended for average risk women of any age

Gail model

Evaluates:

• age

• age of menarche

• age at first live birth

• # of 1st degree relatives w/ breast cancer

• number of previous benign breast biopsies

• atypical benign hyperplasia in previous breast biopsy

• race

assesses 5-year and lifetime risks

BRCA 1 or 2 screening recommendations

Any age to offer treatment decisions, make breast cancer, triple-negative breast cancer, lobular breast cancer, Ashkenazi Jewish ancestry

Unaffected individuals with 1st or 2nd degree blood relatives with specific features

Benefits in early screening

40% reduction in mortality in women 40-83

5 year prognosis for localized breast cancer

99%

5 year prognosis for regional breast cancer

86%

5-year prognosis for distant breast cancer

27%

BI-RADs (breast imaging reporting and data system)

Standardized description and categorization of breast lesions on mammography, US, and MRI with 7 categories with terminology and follow up recommendations

BIRADs 0

Incomplete

BIRADs 6

Malignant

Hormones responsible for breast development

Estrogen

Glandular tissue

Consists of 15-20 lobes with lobules and milk ducts that head toward the nipple and produce breast milk

Lymphatic tissues

75% of lymph flows to the axilla; 25% flower to the paternal LN, abdomen, or breast

2025 Est. new breast cases

316, 950 (32%)

2025 Est. breast deaths

42,170 (14%)

Position as cancer-related death

Second leading cause of cancer death in women

Rates of decline in mortality

1.3% per year

Black women mortality rate compared to white women

41% higher

Incidence rate trends per year

0.5% per year

1 in 8 women develop breast cancer

White

1 in 10 women develop breast cancer

Black

BRCA1 Risk

60% lifetime risk; predisposition to triple-negative breast cancer

BRCA2 Risk

60% lifetime risk; predisposition to ER-positive breast cancers

TP53 Risk (Li-Fraumeni)

60%; predisposition to triple-positive breast cancer

ATM Risk (ataxia-telangiectasis)

15-40%

BARD1 Risk

15-40%; predisposition to triple negative breast cancer

PTEN Risk (Cowden)

40-60%

STK11 Risk (Peutz-Jeghers)

40-60%

CHEK2 Risk

15-40%; predisposition to ER-positive carcinoma

Lynch Syndrome

Hereditary non polyposis colorectal cancer

PALB2 Risk

Partner and localizer of BRCA2; 41-62%; overrepresentation of triple-negative breast cancer

BRIP1 Risk

Potential increase for cancer

RAD51C & RAD51D Risk

15-40%; ER/PR negative cancer

NF1

15-40%; annual mammograms and Breast MRI from 30-50 yo

CDH1

41-60%; predisposition for lobular cancer

Klinefelter syndrome risk

Extra X chromosome causes increased estrogen and decreased androgens

Pregnancy related risk

• Late age of first full-term pregnancy (after 30)

• Nulliparity

• Low birth numbers

• No lactation

• Early menstruation before 12 years and late menopause after age 55

Breast implant related risk

Usually with textured implants, causes Breast-Implant Associated Anaplastic Large Cell Lymphoma

Alcohol associated risk

1pd: 7-10%

2-3pd: 20%

Risk-reducing meds as primary prevention

• Tamoxifen (<1% increased risk cervical CA; pre and post meno; men and women)

• Raloxifene (post meno women)

• Aromatase Inhibitors: Exemestane & Anastrozole (women)

Contraindications for tamoxifen and raloxifene

• DVT history

• PE

• Thrombotic stroke

• TIA

• Known inherited clotting trait

primary prevention - risk reduction surgery

Bilateral mastectomy

When increased screening measures are appropriate

Risk model >20% or genetic variant; annual mammogram 10 years prior to youngest family member dx and MRI w/ contrast 10 years prior (but not < 25 years)

Biomarker tests run if biopsy positive for cancer

ER, PR, HER2, Ki67 status

Invasive ductal carcinoma

80% of all cancer cases; clinical prognosis variable

Invasive lobular carcinoma

10% of all cases; non palpable, difficult to diagnose, more likely to affect bilateral breasts

Subtypes of invasive carcinoma

<5% of cases; most favorable prognosis - papillary, tubular mucinous, medullary carcinoma; less favorable prognosis - metaplastic carcinoma, micropapillary carcinoma, mixed carcinoma

Inflammatory breast cancer

Aggressive and rare; 1-5% of all breast cancers; s/s: edema, erythema, skin thickening, peau d’orange

Paget disease of the breast

Unilateral eczematous changes in the nipple; seen with ductal carcinoma in situ and invasive breast cancer

Cystosarcoma phyllodes

<1% of cases; 90% benign and 10% malignant; rarely metastasizes but can recur

Rare tumors of the breast

Squamous cell, lymphoma, angiosarcoma

Intraductal carcinoma (DCIS)

Noninvasive; surgical excision recommended; not palpable; detected as pleomorphic calcifications; cromedonecrosis is more aggressive and invasive

Lobular carcinoma in situ

Multicentric (2+ tumors) and multifocal(2+ quadrants); incidental finding on breast MRI; surgical excision recommended

Atypical ductal hyperplasia and atypical lobular hyperplasia

Surgical excision recommended

Flat epithelial atypia

High risk breast lesion

Fibroepithelial lesions

High risk breast lesion

Pseudoangiomatous stromal hyperplasia

High risk breast lesion

Sclerosing lesion

High risk breast lesion

Radial scar

High risk breast lesion

Papillary lesions

High risk breast lesion

Luminal A tumors

• ER & PR +, HER2-

• low Ki67 = low grade (<20%)

• favorable prognosis

• Likely to respond to endocrine therapy

• 30-40% of all invasive breast cancers

Luminal B Tumors

• ER+, PR+(low), HER2-

• High Ki67(>14-20%)

• Grade 2 or 3; less well differentiated

• 20-30% of all breast cancers

Luminal B Like Tumors

• ER+, PR±, HER2+

• Any Ki67

HER2-amplified

• amplification of HER2 on chromosome 17q

• Poor clinical prognosis; improved with Trastuzumab

• 12-20% of invasive breast cancers

HER2 Subtypes

HER2 Enriched & HER2 Luminal

HER2 Enriched

ER/PR-, HER2 Positive

HER2 Luminal

ER/PR+, HER2+

Basal tumors

• Triple negative

• Normally BRCA1, young women, & African Americans

• Poor prognosis

• 15-20% of invasive breast cancers

Bloom-Richardson Grade 1

low grade and well differentiated

Bloom-Richardson Grade 2

Intermediate grade or moderately differentiated

Bloom-Richardson Grade 3

High grade or poorly differentiated

Clinical staging

Based on biopsy, physical exam, and imaging

Pathological staging

Based on tissue removed during surgery

TNM

• Size of tumor

• Lymph node involvement

• Presence of metastasis

Stage 0

Noninvasive (DCIS)

Stage 1

Invasive, tumors <2 cm & no LN involvement

Stage 2

Invasive, tumors 2-5cm, some LN involvement

Stage 3

Invasive, heavy burden of breast and axilla LN involvement (inflammatory breast cancer)

Stage 4

Metastasis

Staging work up includes:

• CT if chest (pulm nodules present)

• Abd/pelvic CT or MRI (elevated alkaline phosphatates, abnormal liver function test, abdominal symptoms, Clinical Stage IIa or higher)

• Bone Scan (elevated alkaline phosphatate or bone pain)

• PET or CT (not for all women)

• Bil Breast MRI (optional for stages 1-3)

• CBC, Plt, Liver, Alkaline Phosphatase

Most common sites of metastasis

bone, lungs, brain, and liver(abdomen)

Combined 5 year survival rate

90%

Localized 5 year survival rate

99%

Regional 5 year survival rate

86%

Distant 5 year survival rate

29%

Ki67

Marker of proliferation; <5% or >30% used to estimate prognosis and usefulness of chemotherapy

Breast cancer gene expression testing

Performed on pt’s tumor tissue to assess risk of distant recurrence and guide systemic treatments

OncType DX

• 21-gene assay

• predicts chemotherapy and endocrine therapy benefit

• estimates 10-year risk of distant recurrence

• women with early-stage, ER+, HER2-, LN- or between 1 and 3+ LN, invasive breast cancer

Oncotype DX in Postmenopausal Women

<26 = no benefit from addition of chemotherapy

> or equal to 26 = chemotherapy recommended

OncoType DX in premenopausal women with negative LN involvement

< or equal to 15 = no benefit from additional chemotherapy

16-25 = chemotherapy may be considered

> or equal to 26 = chemo recommended

OncoType DX in premenopausal women with 1-3 positive LN

<26 = consider chemo

> or equal to 26 = chemotherapy recommended

MammaPrint

• 70-gene microarray assay the identifies women with early-stage breast cancer’s risk of distant recurrence in 10 years

• Any hormone receptor or HER2 status

• Results: low or high risk of mets

BluePrint

• Used with MammoPrint

• 80-gene microarray

• Categorizes tumors as Luminal A or B, or Basal

Prosigna

• 50 gene assay assess risk of recurrence and potential response to chemo

• Early stage, ER+ w/wo LN involvement

Endopredict

• 12 gene assay to assess:

• 10 years recurrence risk

• Chemo benefits

• Extended endocrine therapy benefits

• Early-stage, ER+, HER2-, LN- or LN+{1-3}

Breast Cancer Index

• Predicts benefit of additional endocrine therapy (past 5 years) to reduce distant recurrence

• Early-stage, hormone receptor-positive breast cancers

Locoregional treatment of Clinical Stage 1-3, N0 or N+M0 disease

• Breast conserving surgery

• Mastectomy

• Sentinel LN biopsy

• Axillary LN dissection