This document provides information on types and management of breast cancer. It discusses non-invasive and invasive breast carcinomas, including specific types like colloid carcinoma. Prognostic factors are described such as tumor grade and stage. Management of triple negative breast cancer is also covered, noting it is more aggressive and difficult to treat. A new vaccine study aims to prevent triple negative breast cancer.

2. BREAST TUMOURS II
Dr Venugopal Rao MD
PATHOLOGY II

3. Learning objectives
• To learn about remaining types of breast carcinomas.
• To learn in detail about Grading ,staging and prognosis of breast
cancers.
• To learn in detail about management and vaccine of breast cancer of
TNBC

4. A. NON-INVASIVE (IN SITU) CARCINOMA
1. Intraductal carcinoma
2. Lobular carcinoma in situ
B. INVASIVE CARCINOMA
1. Infiltrating (invasive) duct carcinoma-NOS (not otherwise specified) (80%)
2. Infiltrating (invasive) lobular carcinoma (10%)
3. Tubular (cribriform) carcinoma (6%)
4. Medullary carcinoma (2%)
5. Colloid (mucinous) carcinoma (2%)
6. Other types: Papillary carcinoma, adenoid cystic (invasive cribriform)
carcinoma, secretory (juvenile) carcinoma, inflammatory carcinoma,
metaplastic carcinoma
C. PAGET’S DISEASE OF THE NIPPLE.

5. COLLOID (MUCINOUS) CARCINOMA
• This pattern of breast cancer is seen in about 2% cases.
• more frequently in older women and is slow-growing.
• Colloid carcinoma has better prognosis than the usual infiltrating duct
carcinoma.
G/A The tumour is usually a soft and gelatinous mass with well-
demarcated borders.
M/E Colloid carcinoma contains large amount of extracellular epithelial
mucin and acini filled with mucin. Cuboidal to tall columnar tumour
cells, some showing mucus vacuolation, are seen floating in large lakes
of mucin.

6. Colloid carcinoma, microscopic
This variant of breast cancer is known as colloid, or mucinous, carcinoma because of the abundant bluish mucin ( ) shown. The
carcinoma cells (◀) appear to be floating in the mucin. This mucinous matrix gives the tumor a grossly soft, blue-to-gray
appearance. Some of these tumors occur in association with BRCA1 gene mutations. This variant tends to occur in older women
as a small, circumscribed mass. It is slow growing, and when it is the predominant histologic pattern present in a breast cancer,
the prognosis is better than for nonmucinous, invasive carcinomas. They are ER positive and HER2 negative.

7. OTHER MORPHOLOGIC FORMS
1. Inflammatory carcinoma Inflammatory carcinoma of the breast is a clinical entity
and does not constitute a histological type. The term has been used for breast cancers
in which there is redness, oedema, tenderness and rapid enlargement.
2. Adenoid cystic carcinoma Adenoid cystic or invasive cribriform carcinoma is a
unique histologic pattern of breast cancer in which there is stromal invasion by
islands of cells having characteristic cribriform (fenestrated) appearance. The
tumour has an excellent prognosis.
3. Secretory (Juvenile) carcinoma This pattern is found more frequently in children
and young girls and has a better prognosis.
4.Papillary carcinoma It is a rare variety of infiltrating duct carcinoma in which the
stromal invasion is in the form of papillary structures.
5. Metaplastic carcinoma Rarely, invasive ductal carcinomas, besides epithelial
elements, may have various components of metaplastic alterations such as squamous
metaplasia, cartilaginous and osseous metaplasia, or their combinations.

8. PAGET’S DISEASE OF THE NIPPLE
• Paget’s disease of the nipple is an eczematoid lesion of the nipple, often
associated with an invasive or non-invasive ductal carcinoma of the
underlying breast.
• The nipple bears a crusted, scaly and eczematoid lesion with a palpable
subareolar mass in about half the cases.
• palpable mass are found to have infiltrating duct carcinoma, while those
with no palpable breast lump are usually subsequently found to have
intraductal carcinoma.
G/A The skin of the nipple and areola is crusted, fissured and ulcerated with
oozing of serosanguineous fluid from the erosions.

9. Histological examination of Page's disease: Paget's cells, with abundant pale
cytoplasmand pleomorphic nuclei, replace the basal epidermis and are
scattered individually throughout the squamous epithelium.

10. M/E
• The skin lesion is characterised by the presence of Paget’s cells singly or in
small clusters in the epidermis.
• These cells are larger than the epidermal cells, spherical, having
hyperchromatic nuclei with cytoplasmic halo that stains positively with
mucicarmine.
• The underlying breast contains invasive or non-invasive duct carcinoma
which shows no obvious direct invasion of the skin of nip.

11. GRADING, STAGING AND PROGNOSIS
Histologic grading and clinical staging of breast cancer determines the management
and clinical course in these patients.
A. HISTOLOGIC GRADING The breast cancers are subdivided into various histologic
grades depending upon the following parameters:
1. Histologic type of tumour Various microscopic types of breast cancer can be
subdivided into 3 histologic grades:
i) Non-metastasising—Intraductal and lobular carcinoma in situ.
ii) Less commonly metastasising—Medullary, colloid, papillary, tubular, adenoid
cystic (invasive cribriform), and secretory (juvenile) carcinomas.
iii) Commonly metastasising—Infiltrating duct, invasive lobular, and inflammatory
carcinomas.
2. Microscopic grade Widely used system for microscopic grading of breast
carcinoma is Nottingham modification of the Bloom-Richardson system. It is based
on 3 features:
i) tubule formation
ii) ii) nuclear pleomorphism; and iii) mitotic count

12. 3. Tumour size There is generally an inverse relationship between diameter of
primary breast cancer at the time of mastectomy and long-term survival.
4. Axillary lymph node metastasis More the number of regional lymph nodes
involved, worse is the survival rate.
• Involvement of the lymph nodes from proximal to distal axilla (i.e. level I—
superficial axilla, to level III—deep axilla) is directly correlated with the survival
rate.
5. Oestrogen and progesterone receptors (ER/PR)
• Oestrogen is known to promote the breast cancer.
• Presence or absence of hormone receptors on the tumour cells can help in
predicting the response of breast cancer to endocrine therapy.
• Accordingly, patients with high levels of ER and PR on breast tumour cells have
a slightly better prognosis

13. 6. HER2/neu overexpression HER2/neu (also called erbB2), An
individual having overexpression of HER2/neu by tumour cells is likely
to respond to higher dose of herceptin therapy but is not related to
other forms of chemotherapy.
7. DNA content Tumour cell subpopulations with aneuploid DNA
content as evaluated by mitotic markers (e.g. Ki-67) or by flow
cytometry have a worse prognosis than purely diploid tumours.

14. • Mammography (also
called mastography) is the
process of using low-energy X-
rays (usually around 30 kVp) to
examine the human breast for
diagnosis and screening.
The goal of mammography is
the early detection of breast
cancer, typically through
detection of characteristic
masses or microcalcifications.

16. C. PROGNOSTIC FACTORS IN BREAST CANCER These prognostic factors are
divided into following 3 groups:
1. Potentially pre-malignant lesions These conditions are as under:
i) Atypical ductal hyperplasia is associated with 4-5 times increased risk.
ii) Clinging carcinoma is a related lesion in the duct.
iii) Fibroadenoma is a long-term risk factor (after over 20 years).
2. Breast carcinoma in situ Following factors act as determinants:
i) Ductal carcinoma in situ (comedo and non-comedo subtypes) is diagnosed on
the basis of three histologic features—nuclear grade, nuclear morphology and
necrosis, while lobular neoplasia includes full spectrum of changes of lobular
carcinoma in situ and atypical lobular hyperplasia.
ii) Breast conservative therapy is used more frequently nowadays in carcinoma
in situ which requires consideration of three factors for management: margins,
extent of disease, and biological markers

17. 3. Invasive breast cancer These can be broadly divided into 3 groups:
1. routine histopathology criteria;
2. hormone receptor status; and
3. biological indicators.
the most important parameter of node-positive or node-negative breast cancer,
the prognosis varies— localised form of breast cancer without axillary lymph node
involvement has a survival rate of 84% while survival rate falls to 56% with nodal
metastases.
4. Molecular classification More recently, based on gene profiling of breast cancer
by microarray, a molecular classification has been proposed.
It takes into consideration patterns of gene expression by the breast cancer which
may be one of the four types: luminal type A or B, HER2/neu type, basal-like
type, and normal breast-like type. Out of all these, basal-like type has worst
prognosis while luminal type A responds well to endocrine therapy and has good
prognosis.

20. Favourable Poor

22. Triple-negative breast cancer (TNBC)
• is a type of breast cancer that is usually more aggressive, harder to treat, and more
likely to come back (recur) than cancers that are hormone receptor-positive or
HER2-positive.
• Triple-negative breast cancer is invasive breast cancer that is: estrogen receptor-
negative progesterone receptor-negative HER2-negative
• This means the cancer cells don’t have receptors for the hormones estrogen or
progesterone and don’t make too much of the HER2 protein.
• So triple-negative breast cancers don't respond to hormonal therapy medicines or
the medicines that target the HER2 protein.
• About 10-15% of all breast cancers are triple-negative.
• Triple-negative breast cancer is more common in: women younger than 40 Black
women women who have a BRCA1 mutation
• The symptoms, staging, diagnosis, and survivorship care for triple-negative breast
cancer are the same as other invasive ductal carcinomas.

23. Treatments for triple-negative breast cancer
• Surgery
• Radiation therapy
• Chemotherapy
• Immunotherapy
TNBC vaccine
• Researchers at Cleveland Clinic have initiated a first-of-its-kind study of a vaccine
designed to ultimately prevent triple-negative breast cancer — the deadliest form of the
disease.
• The phase 1 study will determine the maximum tolerated dose of the vaccine in patients
with early stage, triple-negative breast cancer and evaluate immune response to the
vaccine.
• The FDA recently approved the vaccine as an investigational new drug, enabling
Cleveland Clinic and partner Anixa Biosciences Inc. to undertake the study.

25. Thank you all