Lecture 33 - Diseases of Breast

Question 1

Which are more likely to be malignant, round or spiculated/irregular densities found on mammography?

Answer 1

Spiculated/irregular

Question 2

BI-RADS scoring system for breast imaging is categorized 0-6.

0 –> basically inconclusive and needs further imaging or comparison to previous imaging

1 –> ______

2 –> _______

3 –> _______

4–> _______

5—> _______

6–> _______

Answer 2

1 –> no abnormal findings

2 –> Benign abnormal findings (non-cancerous calcifications/small round lesion)

3 –> potentially not benign, follow up in less than a year (usually 6 months)

4 –> Potentially malignant, biopsy likely recommended

5 –> Looks malignant, do the biopsy

6 –> Biopsy confirmed malignancy (imaging here is more to check progression and/or treatment efficacy)

Question 3

Similar to colon cancer screening, patients with family hx of breast cancer should have an annual mammogram starting at an age _____years younger than when their family member was diagnosed or starting at age ______ (whichever is sooner).

Patients with known ______ mutations should have annual mammograms starting between ages 25-30.

Answer 3

10 years younger

40

BRCA

Question 4

_______ is the antibiotic of choice for acute mastitis (most often caused by infection with ____ ____ following nipple trauma from breast feeding) because it is not harmful to the child –> this is important because one of the therapies for acute mastitis is to continue breast feeding.

Answer 4

Dicloxacillin

Stapg aureus

Question 5

The biggest risk factor for Squamous Metaplasia of the lactiferous ducts is ______ (90% of patients) –> it is thought this causes a relative Vit___ deficiency that leads to the metaplasia. The squamous cells of the ducts produce _____, which can plug the ducts causing dilation, inflammation, and eventually rupture.

Answer 5

Smoking

Vit A

Keratin

Question 6

A good indicator that abnormal breast tissue is not cancerous is the presence of a fair amount of _______ cells (they decrease in number as the lesion progresses to cancer).

Answer 6

Myoepithelial cells

Question 7

2/3 of breast Fibroadenomas demonstrate mutations in ______ (gene).

Answer 7

MED 12

Question 8

Benign Phyllodes tumors, like Fibroadenomas, typically demonstrate mutations in ______. Those that are malignant may also show mutations in _____.

Answer 8

MED 12

TERT

Question 9

Of Fibroadenomas and Phyllodes tumors, which are common in women in their 3rd decade of life (20’s) and which are common in women in their 5th-6th decades of life (40’s-50’s)?

Answer 9

Fibroadenoma –> 3rd decade

Phyllodes –> 5th-6th decades

Question 10

Black and Hispanic women have lesser risk of developing breast cancer overall, but if they do develop breast cancer before their 5th-6th decades of life, it is usually _____ negative OR ______ positive. It has a worse prognosis, but why?

Answer 10

Triple negative

HER2 positive

It has a worse prognosis bc many of the breast cancer therapies in use today rely on the receptors Triple negative breast cancer lacks (Estrogen, Progesterone, HER2). On the other hand, overexpression of HER2 (HER2 positive) causes out-of-control cell division, so these cancers will be more aggressive.

Question 11

Increased breast density is a risk factor for breast cancer, but one of the reasons relates to imaging. How does breast density affect mammography?

Answer 11

Mammography is LESS effective in MORE dense breasts. MRI is recommended for these patients.

Question 12

Patients with DCIS (Ductal Carcinoma in-situ) have an ____-_____ X greater risk of developing Invasive carcinoma.

Answer 12

8-10 X greater risk

Question 13

What’s the difference histologically between Non-comedo DCIS and Comedo DCIS?

Answer 13

Comedo DCIS (think comedone –> black heads) have a central area of necrosis.

Question 14

Paget’s disease of the nipple arises from DCIS that extend from the _____ ducts to the nipple. Because it mimics ______ (which type of cancer?), it’s important to test the malignant cells to determine if they are breast tissue cells.

Answer 14

Lactiferous ducts

Melanoma

Question 15

Lobular Carcinoma in-situ (LCIS) is almost always found _______ (how?). The arrangement of cells in LCIS is discohesive because the cells lose expression of ____ ______, a cellular adhesion protein.

They almost always express ______ and _______ receptors. What does this typically mean for HER2 expression?

Answer 15

Incidentally

E Cadherin

Estrogen

Progesterone

This means HER2 overexpression is UNLIKELY (so these are typically less aggressive and have better prognosis)

Question 16

Invasive ductal carcinoma is classified as Well differentiated, Moderately differentiated, and Poorly differentiated. What’s the difference?

Answer 16

The presence of prominent tubule formation decreases from Well to Poorly differentiated, and the tumor becomes more of a solid mass of cells with large nuclei.

Question 17

Invasive Lobular Carcinoma, like Lobular Carcinoma in-situ (LCIS), shows loss of expression of _____ _______. These lesions tend to be poorly circumscribed and show a diffuse invasive pattern of cells in a “_____ _____” arrangement.

Answer 17

E Cadherin

“Single file”

Question 18

Where has the cancer invaded when patients present with peau d’ orange appearance of the breast?

Answer 18

Into epidermal lymphatics, from which it can spread all over –> poor prognosis

Question 19

BRCA1 is located on chromosome _____.

BRCA2 is located on chromosome _____.

Breast cancer in patients with mutations in which one, BRCA1 or BRCA2, tends to be Estrogen Receptor (ER) positive? –> remember this is good for treatment with something like Tamoxifen.

Answer 19

17q21

13q12.3

BRCA2

Question 20

______% of double positive (ER+ and PR+) breast cancers respond to hormone therapy, while only _____% of Single positives respond.

_____ positive alone cancers are less likely to respond to CHEMO, whereas DOUBLE negative cancers are more likely to fail Hormone therapy but respond to CHEMO.

Answer 20

80%

40%

ER+ alone –> less responsive to chemo

Question 21

Luminal Breast cancers are _____ positive / _____ negative and are the MOST common.

Answer 21

ER positive / HER2 negative

Question 22

HER2 is an oncogene located on chromosome ______ (like BRCA1). Breast cancer with overexpression of HER2 is the most common subtype among patients with germline _____ (tumor suppressor gene lost in Li Fraumeni syndrome) mutations. _____ (aka trastuzimab) is a monoclonal AB used to treat HER2+ cancer, but not all HER2+ cancers are responsive.

Answer 22

17

p53

Herceptin

Question 23

Mutations in ______ are highly associated with Triple Negative Breast Cancers (TNBC).

Answer 23

p53

Question 24

Why do males ONLY develop Ductal carcinoma?

Keep in mind male breast cancer is usually associated with a ______ mutation, and they are typically _____ positive.

Answer 24

They don’t have lobules!

BRCA2

ER+