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"Breast cancer now represents the most common female malignancy in both the developing and developed world, and is the primary cause of death among women globally"

Epidemiology Of Breast Cancer

Breast cancer is most commonly diagnosed malignancy among women worldwide.

Breast cancer now represents the most common female malignancy in both the developing and developed world, and is the primary cause of death among women globally.

Breast cancer is the second most common cancer with 1.7 million cases (11.9%) reported in 2012, more cases occurring in less developed (883,000 cases) than more developed regions (794,000) worldwide.

Since the 2008 estimates, breast cancer incidence has increased by more than 20%.

It now represents one in four of all cancers in women, while mortality has increased by 14%.

"Breast cancer ranks as the fifth cause of death from overall cancers"

Breast cancer ranks as the fifth cause of death from overall cancers (522,000 deaths, 6.4%) and while it is the most frequent cause of cancer death in women in less developed regions (324,000 deaths, 14.3% of total), it is now the second cause of cancer death in more developed regions (198,000 deaths, 15.4%) after lung cancer.

The incidence of breast cancer dramatically increases from 1971-2010 due to change in life style habits. 1 woman out of 8 is at the risk of getting breast cancer.

In India breast cancer ranked second cancer after cervical cancer. Estimated number of breast cancer cases in women in 2012 was 144,937 (27%) in India.

Different Breast Cancer Types

Breast cancer is a heterogonous disease with different molecular profiles. Different morphological features arises as result of different genetic, epigenetic and transcriptomic alterations in mammary epithelial and stromal cells. 

Breast cancer is the carcinoma mammary epithelial cells which lined lobules or milk duct. Depending upon the site of origin cancer cells breast cancer of two type lobular carcinoma, carcinoma of the lobular epithelial cells and ductal carcinoma originate from the epithelial cells which lined the milk duct.

Types of Breast Cancer 1

Both ductal and lobular carcinomas are further sub classified as invasive and non invasive carcinoma.

Non-invasive carcinoma in which cancer cells still confine to their parental origin site is called ductal or lobular carcinoma in situ.

When cancer cells are spread to surrounding tissue from their parental origin site is called invasive carcinoma.

"Breast cancer is a heterogenous disease with different molecular profiles"

Non invasive carcinoma of two types depending on their origin site as follows:

Ductal carcinoma in situ is a non invasive carcinoma of milk duct epithelial cells which still confined to their parental origin and does not have the potential to metastases.

If not treated DCIS result in the invasive tumor which are difficult to manage.

DCIS range from low grade to high grade tumor including intermediate grade.

Early detection symptoms are lump in the breast fluid discharge from the nipple and rashes on the nipple on breast.

"Ductal carcinoma in situ (DCIS), which accounts for 65,00 (20–30 %) of breast cancers each year"

Ductal carcinoma in situ (DCIS), which accounts for 65,00 (20–30 %) of breast cancers each year and is most commonly diagnosed on screening mammography, traditionally has been managed through a combination of surgery, radiation therapy (RT), and endocrine therapy.

Loss of heterozygosity is noted in more than 70 percent of high-grade ductal carcinomas in situ, as compared with 35 to 40 percent of cases of atypical hyperplasia and 0 percent in specimens of normal breast tissue.

Lobular carcinoma in situ (LCIS) is a carcinoma of the lobule, milk producing gland at the ends of breast duct, which still confined to their parent origin site in lobules is called lobular carcinoma in situ.

Lobular carcinoma in situ (LCIS) is considered to be a risk factor for the development of invasive breast carcinoma, but it may also be a non-obligate precursor to invasive lobular carcinoma (ILC).

LCIS is believed to arise from atypical lobular hyperplasia (ALH).

LCIS is most common among the menopausal women and these women are at 8 to 10 times more risk developing the invasive breast cancer.

Origin of Breast Cancer 6

Invasive ductal carcinoma is the most common type of breast cancer sometimes called infiltrating ductal carcinoma of the milk duct.

This is the largest group of malignant mammary tumors, comprising 75% to 80% of mammary carcinomas.

With invasive cancer, cancer cells start in a milk duct, break through the duct walls, and then invade fatty breast tissue.

Invasive cancer can remain localized, or the cancer cells may enter the bloodstream or lymphatic system and metastasize.

Invasive ductal carcinoma is the most common type of invasive breast cancer and accounts for 75% of all invasive breast cancers.

"Invasive ductal carcinoma is the largest group of malignant mammary tumors, comprising 75% to 80% of mammary carcinomas"

The prognosis of invasive breast cancer is strongly influenced by the stage of the disease, or to what extent the cancer has spread when it is first diagnosed.

Staging takes into consideration size, local involvement, lymph node status and whether metastatic disease is present.

The higher the stage at diagnosis, the poorer the prognosis.

Invasive lobular carcinoma (ILC) is the invasive form of lobular carcinoma some time called infiltrating lobular carcinoma.

About 10% of all invasive breast cancers are invasive lobular carcinomas.

Large studies have shown that approximately 93% of ILC cases are estrogen receptor (ER) positive.

Classic invasive lobular carcinoma (ILC) is characterized histologically by small, discohesive carcinoma cells that infiltrate breast stroma as single cells and in linear files.

"About 10% of all invasive breast cancers are invasive lobular carcinomas"

ILC cells have characteristic plasmacytoid morphology and may also have intracytoplasmic vacuoles and/or signet ring forms.

Morphologic mimics of ILC include both carcinomatous and non-carcinomatous neoplasms, many of which are rarely seen in the breast.

Types of Breast Cancer 3

Breast Cancer Hormone Receptor Status

Steroid hormone receptors have important role in the normal development of breast.

Estrogen receptor (ER), progesterone receptor (PR) and human epidermal receptor 2 (Her2/neu) and androgen receptor (AR) are the main steroid receptors which play important role in initiation and progression of the breast cancer.

At puberty 10% mammary epithelial cells expresses ER while 20% cells expresses androgen receptor (AR).

"ER positive breast cancers expresses the ER in their cells sometime these cancers also expresses PR, Her2/neu and AR"

Normally mammary tissue cells expresses the estrogen receptor in less than 1% cells which are essential for the normal development and differentiation of the terminal ductal cells to milk producing cuboidal cells while in breast cancer the level of estrogen receptor (ER-α) is very high.

Depending upon the expression level of ER in breast cancer tissue breast cancer is classified as:

ER positive Breast cancer (ER +Ve): ER positive breast cancers expresses the ER in their cells sometime these cancers also expresses PR, Her2/neu and AR.

ER positive BC is most common type of breast which accounts for 70-80% all types of breast cancer.

ER positive breast cancers are non invasive tumor which is favorable for its management these tumors are associated with low tumor burden and high survival, good prognosis.

Endocrine based therapies are most effective therapies for ER positive BCs.

"ER positive BC is most common type of breast which accounts for 70-80% all types of breast cancer"

Tamoxifen, a ER antagonist specifically target the ER signaling is the most effective drug for the ER positive breast cancers while it not so effective in ER negative breast cancer cases and associated with hair loss, pain in joints and abnormal menstrual cycle and nausea and vomiting.

ER negative Breast cancer (ER -Ve): ER negative breast cells expresses very low level of ER in their cells.

ER-Ve is aggressive type which has highly invasive and has great potential to get metastases.

ER-Ve BCs account for 20-30 % of all types breast cancers. ER –Ve breast cancer associated with poor prognosis, low survivability, high recurrence and high cost of management.

ER negative breast cancer is further sub classified as triple negative breast cancer, basal like breast cancer and apocrine breast cancers.

Triple negative breast cancer (TNBC) is negative for all the three steroid receptors (ER, PR and Her2/neu) which account 10-15 % of all breast cancers among women.

Triple negative breast cancer are most dangerous and highly aggressive type of tumor with greater invasive and metastatic potential.

"ER –Ve breast cancer associated with poor prognosis, low survivability, high recurrence and high cost of management"

Molecular apocrine breast cancer which is negative for ER and PR and Her2/neu and positive for AR had phenotypic characteristics similar to that of ER positive breast cancer.

Molecular apocrine tumor also expresses GHR, EGFR receptors and PRLR.

These tumors account for 4-14% of all types of breast cancers.

Molecular apocrine breast cancer further sub classified as luminal (ER + AR +), apocrine (ER-AR +) and basal (ER- AR-).

Origin of Breast Cancer 5

Depending upon the expression profile of the steroid hormone receptors and erythroblastosis oncogene B2 (ERBb2 or Her2/neu) breast cancer is classified as Basal like, Luminal A, Luminal B and Her2/neu rich breast cancer.

Basal like tumor are ER, PR and Her2/neu negative and expresses one or more cytokeratin markers 5/6, cytokeratin 17, cytokeratin 14 and EGFR and account 10-15% of all breast cancer.

"Triple negative breast cancer are most dangerous and highly aggressive type of tumor with greater invasive and metastatic potential"

Most of the basal like tumor are IDC-NST type with high tumor grade and triple negative phenotype.

71% of triple-negative cancers were of basal-like subtype and only 77% of molecular basal like tumors were triple-negative.

Luminal A breast cancer is ER, PR positive and Her2/neu negative breast cancer while Luminal B is ER, PR and Her2/neu positive.

Luminal B and Luminal A are hormone receptor positive breast cancer which accounts 70% of all breast cancers.

Inflammatory breast cancer (IBC) is a lethal form of breast cancer associated with inflammation of breast tissue which accounts 1-5% of all breast cancer.

Inflammatory breast cancer is type of invasive ductal carcinoma in which duct is filled with fluid due to blockage of duct result in inflammation.

"Inflammatory breast cancer is a lethal form of breast cancer associated with inflammation of breast tissue which accounts 1-5% of all breast cancer"

IBC characterised by inflammation, redness which covers more than 30% of the total mammary gland and “peau d’orange” appearance and at molecular level by loss of WNT1-inducible-signaling pathway protein 3 (WISP3) signalling and increased expression of E-cadherins and C-guanosine triphosphatase (RhoCGTPase).

Most of the IBC are of grade IV. de Andrés PJ et. al 2013 reported increased level of cytokines IL-6, IL-8 and IL-10 play important role in the inflammatory breast cancers.

With the use of neoadjuvant therapies for the IBC patient survival rate had increased from 30% to 42% and in 70-80% in non IBC patients.

Male breast cancer (mBC) is a rarest type of mammary tumor among male is male breast cancer (mBC) which account ∼1% of all cancer in men.

Hormone receptor positivity (70-90 %) is more in mBC than FBC (60-70%) and lower Her2 over expression.

Biologically mBC differ from FBC and showed lower metastatic tumor profile and chemotherapy, Endocrine therapy and trastuzumab are effective and safe for mBC.

TNM Staging and grading system of Breast cancer

The severnity of the disease breast cancer is grouped into differnt stage diseases in term of its tumor size, number lymph nodes positive for the breast cancer cells, whether breasst cancer cells get metastasses or not metastatic.

"TNM is a standard way of representing the tumor stage and determining tumor grades"

TNM is a standard way of representing the tumor stage and determining tumor grades.

T represent the size of tumor when the size of tumor is less than 1cm the T is represented as T1 which further specified into different category as T1mi, T1a, T1b and T1c as shown in the figure. when tumor size range 2-5 cm it is represented as T2 and when it is more than 5 cm it is represented as T3.

Any size of tumor which as invade to the breast bone is represented as T4 which is further sub categorized as shown in the figure.

The number of nodes positive for the breast cancer cells is represented in terms of N.

When breast cancer cells are get metastases to distant organs from their parental origin it is represented as M1.

Finally the grades of the tumor are determine as according to the TNM status.

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