Neoplastic Disease Of The Breasts

Question 1

Two types of stroma in the breast

Answer 1

Interlobular and intralobular
- each give rise to different types of neoplasms

Intralobular

• hemangioma
• angiosarcoma

Interlobular

• fibroadenoma
• phyllodes tumor

Question 2

Breast carcinoma

Answer 2

Most common malignancy of women’s globally and causes majority of cancer deaths in women

Lifetime risk = 1:8 of all women living to age 90

95% = adenocarcinomas

Incidence in men = 1% compared to women rates

75% of women with breast cancer are > 50 yrs of age
- only 5% are <40 and almost always have BRCA1 mutations

Question 3

Classification system of carcinomas of the breast

Answer 3

Based on expression of hormone receptors on the cancer

1) estrogen receptor (ER) positive
- HER2 (-)
- makes up 50-60% of breast cancers

2) ER and human epidermal growth receptor 2 (HER2) positive
- makes up 10-20% of cancers

3) triple negative (ER,PR,HER2 (-))
- makes up 10-20% of cancers

Question 4

Known risk factors for breast carcinoma

Answer 4

Germline mutations in BRCA1/2 = 45x risk
- is a tumor suppressor gene specific to breast carcinoma

Family history of any breast cancer

Hispanic/blacks = rarer but if they get breast cancer its more likely to be aggressive

White/European = more likely to get breast cancer but its more likely to be less aggressive

Living in America or Europe

Early menarche

Late menopause

Late pregnancies

Presence or any benign breast disease
- carcinoma in situ and with atypia are the two highest risk

Use or ionizing radiation

• ONLY when the breast is still developing
• 25-30% of Hodgkin lymphoma 10-20s women who undergo radiation get breast cancer
• however Hodgkin lymphoma patients older than 30 with radiation = no increase

Using HRT or obestiy in menopause

Alcohol consumption

Question 5

What are known protective factors against breast cancer

Answer 5

First pregnancy before 20 yrs old

Beast feeding children

Question 6

BRCA1 and BRCA2

Answer 6

Classic breast cancer tumor suppressor genes
- ONLY causes cancer if both are knocked (however only one needs to mutated)

Both encode proteins to repair DNA damage
- activates the RAD51-recombinant enzymes at DNA damage sites to repair it

BRCA1 mutations = triple negative cancers

BRCA2 mutations = ER-positive tumors

Question 7

Estrogen in carcinoma of the breast

Answer 7

Increases risks for metals is in these cancers

- stimulates production of growth factors which speeds up breast cancer growth

Question 8

Most common locations of breast carcinoma

Answer 8

50% = upper outer quadrant

20% = central portion

30% = anywhere else

Question 9

Grades of invasive breast carcinoma

Answer 9

Grade 1 - grade 3

is based on nuclear pleomorphism, tubule formation and proliferation

Low grade nuclei = similar to normal cells

High grade nuclei = enlarged and irregular nuclei

Question 10

Clinical features of carcinoma of the breast

Answer 10

In unscreened (younger) populations = palpable mass is the first symptom

• almost all of these carcinomas are invasive and typically 2-3 cm in size (or higher)
• also 50% will have spread to regional lymph nodes at diagnosis

In screened (older) populations = abnormal mammogram is most common

• 20% = in situ carcinomas
• are usually 1-2cm and only 15% chance of metastasis to regional lymph nodes

Question 11

Factors that influence outcome of breast carcinoma

Answer 11

Biological type

• grade
• histological appearance
• expression of HER2
• any hormone receptors present

RNA expression profiling

Tumor stage = based on primary tumor (T), involvement of regional lymph nodes (N) and presence of metastasis (M)

• T1 -3 = size only
• T4 = ulceration of the skin is present

Question 12

Treatment of breast carcinoma

Answer 12

No treatment = dies in 3-4 years

80% with treatment survive though

• radiation
• surgery
• tamoxifen (estrogen inhibitor)
• aromatase inhibitors

Question 13

Common sites of metastatic disease

Answer 13

Bone and soft tissue

• most common
• typically respond to endocrine therapy

Visceral tissues (lung, liver) 
- requires chemotherapy 

Brain
- commonly seen with HER2 positive disease

Question 14

TNM staging for breast cancers

Answer 14

Tumor size:

• T1 = <2cm
• T2 = 2-5cm
• T3 >5cm

Nodal status

• N0 = none
• N1 = 1-3 lymph nodes
• N2 = 4-9 lymph nodes
• N3 = 10+ lymph nodes

Metastasis = yes or no
- immediately becomes stage 4 if yes

• *also**
• receptor status
• neamopausal status

Question 15

Treatment for breast cancers based on stages

Answer 15

Stage 1/2 = cure
- radiation if:
Lumpectomy, tumor >5cm, + lymph nodes

Stage 3 = cure

• lumpectomy or mastectomy + axillary lymph node dissection
• chemotherapy
• radiation

Stage 4 = palliative

• maintain QOL
• median survival = 3 years