BREAST CANCER

Robert Miller MDwww.aboutcancer.com

• Breast cancer most common cancer in women (29% cases)• Life time risk of 12.38% (one in eight)• Median age at diagnosis is 61 but (5% 30s, 18% in 40’s, 25%

50’s)

Age Distribution 5 Year Survival by Stage

What You Need to Understand About Breast Cancer Before Deciding on Treatment

What You Need to Know About Breast Cancer Before Deciding on Treatment

• Understand the basic anatomy (lobules, ducts and lymph nodes)• Breast imaging studies (mammograms or ultrasound) CT, MRI, PET• Stage (particularly lymph node status)• Biopsy or pathology report tell you about the biology (how aggressive) of

the cancer

1. Pectoralis Muscle, 2. Fatty Breast Tissue, 3. Breast Cancer, 4. Breast Glands (lobules), 5. Milk Ducts

Internal mammarysupraclavicular

axillary

Lymph Nodes

The tail of thebreast may extendhigh into theaxilla

Imaging

Imaging

a case of advanced cancer… 3 views of the same tumor in a woman with a 2.7 cm breast cancer

Most women are diagnosed at an early stage with abnormal calicifications on their mammogram

Mammograms may often show areas of calcification, which can be benign or malignant

Mammograms may often show areas of calcification, these may be malignant. In ductal carcinoma in situ (DCIS), there is normally no mass but just an area of calcification

Micro-calcifications can be very subtle

Biopsy of this area showed 8mm DCIS

Biopsy = DCIS with focal micro-invasion

Larger area of micro-calcifications may have invasive cancer

Path = 2.9 cm area of high grade DCIS plus invasive ductal cancer

fat

gland

Breast MRI Scan

In a woman with dense breasts, the mammogram was normal but the MRI showed the cancer

Breast MRI

Path = 2.2 cm cancer in right breast, left breast was benign (False positive?)

benign

Breast MRI

Will show the breast tumor as well as the lymph nodes

Mastectomy = 6cm lobular cancer with 41 out of 42 lymph nodes positive for cancer spread

Breast MRI Scan

A = BreastB = axillaC = internalmammary nodes

CT Scan Anatomy

PET Scan Anatomy for Breast Cancer

PET - CT Scan Anatomy - Reconstruction

Small relapse on the reconstructed right breast, just above the implant

PET Scan: previous right mastectomy but cancer has recurred arising from the rib

PET Scans are usually reserved for more advanced cases of breast cancer

PEM (Positron Emission Mammography)

Sentinel Node Technique and Biopsy

Sentinel Node

Sentinel Node Technique

Breast cancer

nodes

Stage is based on the tumor size (T1 – T4)

T 0 = DCIS T1 = 2cm T2 = > 2 – 5cm T3 = > 5cm

N0 = no nodes N1 = 1 -3 nodes N2 = 4 – 9 nodesN3 = 10 nodes or SCV or IMC

Stage is based on lymph node spread (N1 – N3)

Odds of Spread to Sentinel Node

Tumor size in cm

Grade and LV invasion

The bigger the tumor the more likely it has spread to the lymph nodes

If the biopsy shows a more aggressive form of cancer (high grade cancer) or cancers cells are seen in vessels (LV) then there is a high chance the cancer has spread to the nodes

Breast Cancer Stage

So the stage if based on both the tumor size or the lymph node status, so stage IIB would be T2N1 or T3N0

N1 T2

T3

N0

Mortality based on size of cancer and number of lymph nodes involved

Tumor size in cm

6 + Nodes

3 + Nodes

0 + Nodes

Mortality based on cancer grade for node negative and node positive cancers

Cancer Grade

2cm tumor with 3 + nodes

2cm tumor with 0 + nodes

Understanding a Pathology Report

1. Invasive or Not (DCIS, LCIS)

2. Histology: what type of cancer

3. Grade: fast or slow growing

4. Hormone Receptors: is it sensitive to estrogen or progesterone

5. HER2 (human epidermal growth factor receptor 2) a genetic mutation

ductal cells

ductal carcinoma In situ (DCIS)

Invasive ductal carcinoma

20% of breast cancers in the US are stage 0 or non-invasive (ducal carcinoma in situ DCIS or lobular carcinoma in situ LCIS)

Earliest form of cancer is often DCIS (ductal carcinoma in situ) then it progresses to invasive ductal carcinoma

DCIS – Ductal Carcinoma In Situ

Histology Common Aggressive

Invasive Ductal 50 – 75% Average

Invasive Lobular 10 – 15% Average

Medullary 1 – 5% More

Mucinous (colloid) 1 – 5% Less

Papillary (<1%) Less

Tubular (1 – 5% Less

Types of Invasive Breast Cancer

Cancer Cell

A genetically altered or mutated normal cell that results in uncontrolled growth and spread

If the cell has not mutated too much it almost looks like a normal cell (and would be called low grade or well differentiated) would probably still have a normal response to estrogen and be less aggressive (less likely to spread or grow rapidly)

Breast Cancer Grade

Grade Description 5Y Survival

1 (low) Well-differentiated, slow growing 95%

2 (most common) Moderately formed 75%

3 (high) Poorly formed, aggressive 50%

Hormone Receptors

Normal breast cells are sensitive to hormones (estrogen and progesterone) and have chemical receptors that the hormones attach to. About 60 to 70 % of breast cancer cells with still have these receptors.

This is good for two reasons:

1. The cancer cells are less mutated (or dangerous) and the patient's prognosis (outlook) is better

2. Instead of just chemotherapy the woman may benefit from a hormone blocking drug like Tamoxifen (if she’s premenopausal) or an aromatase inhibitor like Femara, Aromasin or Arimidex

HER2 (Human Epidermal Growth Factor Receptor Type 2)

About 20 to 30% of the cancers will have the genetic mutation that leads to abnormal function of the HER2 gene. This is considered a more serious type of cancer but there are antidote drugs available like Herceptin (trastuzamab) against these cells

HER2 (Human Epidermal Growth Factor Receptor Type 2)

Gene expression array methodology

A) RNA from a tumor probes for thousands of genes have been affixed. B) The red (relative overexpression in tumor) and green (relative underexpression in tumor) intensities can be analyzed simultaneously. C) Depending on the supervision of the analysis, tumors can be subtyped (as shown here), or can be analyzed for gene sets associated with clinical outcome.

Genetic ProfilesMay show that some women with favorable breast cancer (estrogen + and node -) may need more than just Tamoxifen / analyze the cancer for the presence (expression of 21 breast cancer genes)

Genetic ProfilesMay show that some women with favorable breast cancer (estrogen + and node -) may need more than just Tamoxifen

27% of women had a high risk gene profile and 30.5% relapsed after Tamoxifen and they may have done better with chemotherapy

MammaPrint is the first and only FDA-cleared IVDMIA breast cancer recurrence assay. The unique 70-gene signature of MammaPrint provides you with the unprecedented ability to identify which early-stage breast cancer patients are at risk of distant recurrence following surgery, independent of Estrogen Receptor status and any prior treatment. Unlike previous generation genomic tests, MammaPrint interrogates all of the critical molecular pathways involved in the breast cancer metastatic cascade. It analyzes 70 critical genes that comprise a definitive gene expression signature and stratifies patients into two distinct groups — low risk or high risk of distant recurrence.  With MammaPrint, there are no intermediate results. Hormonal therapy alone (e.g. Tamoxifen) may be sufficient to further reduce her risk if your patient is Low Risk by MammaPrint, when combined with traditional risk factors. Conversely, if she is High Risk by MammaPrint and has additional risk variables, more aggressive therapy including chemotherapy may be recommended.

BREAST CANCER

Robert Miller MDwww.aboutcancer.com