Breast tumors

BREAST TUMORS

Ch. 18 p (704 – 713)

LYMPHATIC DRAINAGE AXILLARY (MOSTLY) INTERNAL MAMMARY SUPRACLAVICULAR

Fibroadenoma

Cleft

Fibroadenoma

Intraductal papilloma

Cystosarcoma phyllodes
Phyllodes tumor
arises from the interlobular stroma, In contrast to fibroadenomas, it is uncommon & is often larger in size and more cellular.
Projections of stromabetween the ducts create the leaflike patternfor which these tumors are named (from theGreek word phyllodes, meaning “leaflike”).


One in eight women will get breast cancer, and one third of women with breast cancer will die of the disease

Causes of Breast Cancer

Hormonal Genetic Environmental

Risk Factors for Breast Cancer

Estrogen, (F / M = 100 / 1)Menstrual history & Reproductive history. - Long & Strong exposure; (Early menarch & late Menopause) - Pregnancy; (Nilliparous, Late 1st pregnancy) - Lactation, decrease risk - Oophorectomy (decrease the risk to 1/3) Age (Peak; 60 – 70y)Family historty; (1st degree, early age, bilat)/ 2 folds Benign breast disease (Hx of previous breast pathology) - Fibrocystic disease +/- epith hyperplasia +/- atypia. - CIS - 0X, 2X, 5X, 10XGeographyIn 2002 Estrogen declared as carcinogen by National Toxicology Program

The two most common risk factors for breast cancer are: Being female Getting older Breast Cancer (C50): 2011-2013

Other Risk Factors for Breast Cancer

Oral contraceptive Radiation Exposure Carcinoma of the contralateral breast or endometrium Obesity High fat diet Alcohol Smoking Environmental Toxins Breast augmentation. ABORTIONS?

Genetic changes

Proto-oncogen HER2/NEU - 30% - Poor prognosis RAS & MYC Tumor suppressor gene Rb, p53, ER gene inactivation

Gene profiling of breast cancer1. ER +ve, HER2 –ne2. ER +ve, HER2 +ve3. ER -ne, HER2 +ve4. ER -ne, HER2 –neDifferent Outcome & Therapy.

Genetic FactorsInherited Mutations (10%)

10% breast cancers are familial - 90% are sporadic Positive Family History, especially in 1st degree relatives (mother, daughter, sister) confers increased risk for breast cancer Tumor suppressor genes (BRCA1, BRCA2) Risk is greatest with: First degree relative relatives with BILATERAL disease relatives affected at a YOUNG AGE


BRCA1 Gene (17q21)“Breast-Ovarian” cancer gene“Early onset” breast cancer gene High grade breast Ca. Responsible for up to 50% of “inherited” breast cancers, (5% of all breast cancers)BRCA2 Gene (13q); “Male Breast Cancer” gene

Breast Cancer Pathology

Ductal Ca. (85 – 93%)Lobular Ca. (7 – 15%)In Situ Carcinomas (CIS) (15 )Invasive Carcinomas (85%)Special Subtypes (> 5%)

Ductal Carcinoma in Situ

Clinical: DCIS usually does not present as a palpable mass. Mammogram: The most common method of detection is by identifying mammographic calcifications MRI FNA Biopsy

Mammography showing a normal breast (left) and a cancerous breast (right). Mammography is the standard for detection of DCIS. MRI could help especially in high-grade DCIS
Calcification, 50 - 60% in ca. 20% in benign

Micropapillary

Cribriforming DCIS
Comedoca
DCIS

Lobular carcinoma in situ

Multicentric , Bilateral

Invasive Duct Ca

90% of infiltrating breast carcinomas

Infiltrating Ductal Carcinoma

Gross: Firm & gritty, pale - white Micro: Grading; tubule formation nuclear grade mitotic rate - Desmoplastic stromal response (fibrosis).

Infiltrating Lobular Carcinoma

2nd most common invasive breast ca.Multifocal & bilateralSame prognosis as infiltrating ductal ca, when matched for stage- Single cells & linear profiles of malignant cells with “Indian file pattern” - Dense fibrous tissue.

Invasive lobular carcinoma

Invasive ductal carcinoma

Infiltrating ductal ca. Tubular type V. Good prognosis

Infiltrating ductal ca. Medullary type (lots of lymphocytes) better prognosis
Infiltrating ductal ca. Mucinous type Good prognosis
Infiltrating ductal ca. Mucinous type Good prognosis


Peau d’orange of involved skin caused by lymphatic involvement and obstruction. Inflammatory Carcinoma invasive carcinoma involving superficial dermal lymphatic. Erythema & induration
Inflammatory carcinoma: dermal lymphatic spaces containing tumor cells



Paget’s Disease Invasion of the SKIN of nipple or areola by malignant cells. Associated with in situ or invasive ca erythema, scaling, ulceration
Intra-epidermal malignant cells

Extramammary Paget disease

Tumor grade
HISTOLOGY WHO grading Well differentiated Mod. differentiated Poor differentiated B-R grading Glands Nuclei Mitosis
CYTOLOGY Nuclei Size Membrane Chromatin Nucleoli
Nuclear grade 1-3 Good correlation with histologic grade

BREAST CANCERTNM stage grouping

Stage 0 Tis N0 M0 Stage I T1* N0 M0 Stage IIA T0 N1 M0 T1* N1** M0 T2 N0 M0 Stage IIB T2 N1 M0 T3 N0 M0 Stage IIIA T0, T1,* T2 N2 M0 T3 N1, N2 M0 Stage IIIB T4 Any N M0 Any T N3 M0 Stage IV Any T Any N M1
* Note: T1 includes T1 mic.** Note: The prognosis of patients with N1a is similar to that of patients with pN0.

BREAST CANCERTNM stage grouping

TXPrimary tumor cannot be assessedT0No evidence of primary tumorTisCarcinoma in situ: Intraductal carcinoma, lobular carcinoma in situ, or Paget’s disease of the nipple with no tumorT1Tumor 2 cm or less in its greatest diameterT1mic Microinvasion more than 0.1 cm or less in its greatest diameterT1aTumor more than 0.1 cm but not more than 0.5 cm in its greatest diameterT1bTumor more than 0.5 cm but not more than 1 cm in its greatest diameterT1cTumor more than 1 cm but not more than 2 cm in its greatest diameterT2Tumor more than 2 cm but not more than 5 cm in its greatest diameterT3Tumor more than 5 cm in its greatest diameterT4Tumor of any size with direct extension to (a) chest wall or (b) skin, only as described belowT4aExtension to chest wallT4bEdema (including peau d’orange) or ulceration of the skin of the breast or satellite skin nodules confined to the same breastT4cBoth (T4a and T4b)T4dInflammatory carcinoma

BREAST CANCERCommonly assessed prognostic factors

Slamon DJ. Chemotherapy Foundation. 1999;46. Winer E, et al. Cancer: Principles & Practice of Oncology. 6th ed. 2001;1651-1717.
Nuclear grade Estrogen/progesteronereceptors HER2/neu overexpression
Number of positive axillary nodes Tumor size Lymphatic and vascular invasion Histologic tumor type Histologic grade Molecular changes

BREAST CANCER5-year survival as function of the number of positive axillary lymph nodes

0%
20%
40%
60%
80%
5-Year Survival
0
1
2
3
4
5
6-10
11-15
16-20
>20
Number of Positive Nodes
Harris J, et al. Cancer: Principles & Practice of Oncology. 5th ed. 1997;1557-1616.

Histopathologic Grade

If B-R score is 3, 4, 5 = low grade If B-R score is 6, 7 = Intermediate grade If B-R score is 8, 9 = High grade

Histologic grade

BREAST CANCER5-year survival as function of tumor grade

c-erbB-2 (HER-2/neu)

Oncogene which shares extensive sequence homology with epidermal growth factor receptor (EGFR)

Total Cancers

Per Cent
In Situ Carcinoma *
15–30 Ductal carcinoma in situ, DCIS
80
Lobular carcinoma in situ, LCIS
20
Invasive Carcinoma
70–85 No special type carcinoma ("ductal")
79
Lobular carcinoma
10
Tubular/cribriform carcinoma (Better prognosis than average)
6
Mucinous (colloid) carcinoma (Better prognosis than average)
2
Medullary carcinoma (Better prognosis than average)
2
Papillary carcinoma
1
Metaplastic carcinoma, (Squamous)


The “Triple Test”:Clinical pictureMammographic findingsCytologic findings

MALE BREAST

GYNECOMASTIA (related to hyperestrogenism)

Gynecomastia

Reversible enlargement of male breastUnilateral or bilateral subareolar mass +/-painDuctal and stromal proliferation, NO lobulesEtiology - Systemic disease –hyperthyroidism, cirrhosis, CRFDrugs; cimetidine, digitalis, tricyclic antidepressants, marijuanaNeoplasms -pulmonary, testicular germ cell tumorsHypogonadism: testicular atrophy, exogenous estrogen, Klinefelter’s syndrome Periductal edema
Epithelial hyperplasia

THE MALE BREAST

 CarcinomaVery rare occurrence; female cancer to male cancer ratio approx 100:1Pathology and behavior is similar to cancers seen in women although with less breast tissue, skin involvement is more frequent Associated with inherited BRCA2 mutation

Lecture ObjectivesCan you?

1. Discuss the etiology/pathologic features of different forms of benign non-neoplastic and neoplastic breast disease.2. List the benign breast diseases that increase a patient’s risk of developing breast cancer and classify these conditions by the degree of risk.

Lecture ObjectivesCan you?

3. Outline other risk factors predisposing to breast cancer & incidence/prevalence of breast cancer. 4. Classify breast cancer into histologic subtypes and describe the pathologic features of each. 5. List the prognostic factors for breast cancer.