Page 775 - Textbook of Pathology, 6th Edition

About 20% of phyllodes tumours are histologically 1. Geography. The incidence of breast cancer is about six 759
malignant and less than half of them may metastasise. times higher in developed countries than the developing
countries, with the notable exception of Japan. These
INTRADUCTAL PAPILLOMA geographic differences are considered to be related to
consumption of large amount of animal fats and high caloric
Intraductal papilloma is a benign papillary tumour occurring diet by Western populations than the Asians (including
most commonly in a lactiferous duct or lactiferous sinus near Japanese) and Africans.
the nipple. Clinically, it produces serous or serosanguineous
nipple discharge. It is most common in 3rd and 4th decades 2. Genetic factors. Recently, much work has been done on
of life. the influence of family history and inherited mutations in
breast cancer:
MORPHOLOGIC FEATURES. Grossly, intraductal papil- i) Family history: First-degree relatives (mother, sister,
loma is usually solitary, small, less than 1 cm in diameter, daughter) of women with breast cancer have 2 to 6-fold
commonly located in the major mammary ducts close to higher risk of development of breast cancer. The risk is
the nipple. Less commonly, there are multiple proportionate to a few factors:
papillomatosis which are more frequently related to a Number of blood relatives with breast cancer.
papillary carcinoma. Younger age at the time of development of breast cancer.
Histologically, an intraductal papilloma is characterised Bilateral cancers.
by multiple papillae having well-developed fibrovascular High risk cancer families having breast and ovarian
stalks attached to the ductal wall and covered by benign carcinomas.
cuboidal epithelial cells supported by myoepithelial cells. ii) Genetic mutations: About 10% breast cancers have been
An intraductal papillary carcinoma is distinguished from found to have inherited mutations. These mutations include
intraductal papilloma in having severe cytologic atypia, the following, most important of which is breast cancer
pleomorphism, absence of myoepithelial cells, multi- (BRCA) susceptibility gene in inherited breast cancer:
layering and presence of mitotic figures. BRCA 1 gene located on chromosome 17, a DNA repair
gene, is implicated in both breast and ovarian cancer in
CARCINOMA OF THE BREAST inherited cases. BRCA1 deletion is seen in about two-third CHAPTER 25

Cancer of the breast is among the commonest of human of women with inherited breast cancer having family history
cancers throughout the world. Its incidence varies in different but BRCA1 mutation is uncommon in sporadic cases. The
countries but is particularly high in developed countries. In protein product of BRCA gene is a cell cycle regulated protein
the United States, carcinoma of the breast constitutes about and it can be detected by immunohistochemistry. Men who
25% of all cancers in females and causes approximately 20% have mutated BRCA1 have increased risk of developing
of cancer deaths among females. However, there has been cancer of the prostate but not of male breast.
some decline in mortality from the breast cancer in recent BRCA 2 gene located on chromosome 13, another DNA The Breast
years in North America, Western Europe and Australia due repair gene, in its mutated form, has a similarly higher
to both early diagnosis and modern therapy. Cancer of the incidence of inherited cancer of the breast (one-third cases)
male breast, on the other hand, is quite rare and comprises and ovary in females, and prostate in men.
0.2% of malignant tumours (ratio between male-female breast In both BRCA1 and BRCA2, both copies of the genes
cancer is 1:100). The incidence of breast cancer is highest in (homozygous state) must be inactivated for development of
the perimenopausal age group and is uncommon before the breast cancer.
age of 25 years. Mutation in p53 tumour suppressor gene on chromosome
Clinically, the breast cancer usually presents as a solitary, 17 as an acquired defect accounts for 40% cases of sporadic
painless, palpable lump which is detected quite often by self- breast cancer in women but rarely in women with family
examination. Higher the age, more are the chances of breast history of breast cancer. p53 mutation is also seen in Li-
lump turning out to be malignant. Thus, all breast lumps, Fraumeni syndrome having multiple cancers including
irrespective of the age of the patient must be removed breast cancer in young women; others are tumours of the
surgically. Currently, emphasis is on early diagnosis by brain, sarcomas, and adrenal cortical tumours.
mammography, xero-radiography and thermography. Other mutations seen less frequently in breast cancer
Techniques like fine needle aspiration cytology (FNAC), include ataxia telangiectasia gene, PTEN (phosphate and
stereotactic biopsy and frozen section are immensely valuable tensin) tumour suppressor gene.
to the surgeon for immediate pathological diagnosis. 3. Oestrogen excess. There is sufficient evidence to suggest
that excess endogenous oestrogen or exogenously
administered oestrogen for prolonged duration is an
Etiology
important factor in the development of breast cancer.
Though extensive clinical and experimental research as well Evidences in support of increased risk with oestrogen excess
as epidemiologic studies have been carried out in the field are as follows:
of breast cancer, its exact etiology remains elusive. However, i) Women with prolonged reproductive life, with menar-
based on current status of our knowledge, the following risk che setting in at an early age and menopause relatively late
factors are considered significant in its etiology: have greater risk.
ii) Higher risk in unmarried and nulliparous women than
in married and multiparous women.