Breast Carcinoma Types Staging Diagnosis Treatment

Cancer is unique in the staggering numbers of variants it has. cancer originates from the body's own cells- if a cell can divide, it has the capability of developing into a cancer. Being so different in characteristics from each other, different cancers of even the same organ can have different appearances, prognoses, behaviors, aggression, treatment response and even chance of recurrence. Two cancers, both originating in the breast for instance, may have different gene mutations and because of that, one may be survivable and the other may not.

What is Breast Cancer?
breast cancer arise from the inner lining of milk ducts, or lobules (glands) that supply the ducts with milk in the breast. Both these structures makeup the glandular tissue in the breast, while fat and fibrous connective tissue constitute stromal tissue.

Attention to Indications of Breast Cancer
New lump in the breast or in armpit
Unusual pain in the breast or armpit
Irritation of the breast skin
Redness in the breast area
Nipple discharge other than breast milk, including blood
Sunken or inverted nipple
Change in the size or shape of the breast
Peeling or scaling of skin in the breast area

Breast Cancer Risk Factors
Ageing
The risk for breast The risk for breast cancer increases with age. Majority of the cases are
Genetic mutation diagnosed in women aged 50 or above.
Genetic mutation Breast cancer cases are thought to be hereditary, resulting directly from gene defects (genetic mutations) inherited from parents.
Family history Risk for breast cancer is higher among women whose first degree relatives such as mother, sister, daughter or first degree male relatives have this disease. Also the chances are higher if multiple family members from paternal and maternal side are suffering from the same.

Early menstrual period
Women who start their menstrual cycle at the age of 12, are at a higher risk of breast cancer to some extent.
Late or no pregnancy Having a first pregnancy after the age of 30 or never having a full term pregnancy slightly increases breast cancer risk.
Being overweight after menopause Elderly women who are overweight have higher chances of developing breast cancer than those at a normal weight after menopause.
Dense breast tissue issue than fatty tissue and have a high risk of developing breast cancer. In such cases, it is hard to identify tumours on mammogram.
Previous chest radiation Women who had past history of radiation therapy to the chest area for other cancers like Hodgkin disease or Non-Hodgkin lymphoma are at higher risk for breast cancer.
Diethylstilbestrol (DES) exposure During the period of 1940 - 1960, some pregnant women were given the drug diethylstilbestrol, considering it to lower the chances of miscarriage. regnant women or women whose mothers were administered with DES during pregnancy are at higher risk for breast cancer.

How are breast cancers classified?
Classification of breast cancers is done by identifying Histological appearance
Place of origin-ducts (ductal) or lobules (lobular) of the cancer
Whether the tumor remains limited to one component of breast without spreading to surrounding tissue (carcinoma in situ), or has spread to nearby stromal tissue as well (invasive carcinoma).

Therefore, breast cancers can be ductal in situ, ductal invasive, lobular in situ, lobular invasive, among other types. The vast majority (95%) of malignant breast cancers are adenocarcinomas. By definition, adenocarcinomas are cancers that originate in glands.

Precancerous Breast Lesions Precancerous breast tumors are those that have a risk of developing into invasive carcinoma, but are themselves not cancers. Precancerous lesions can be identified by biopsy followed by tissue examination. It is important to identify which of the lesions will develop into invasive carcinomas, so as to avoid overtreatment or undertreatment.

Examples of Precancerous Lesions Lobular Carcinoma In Situ (LCIS) LCIS is a pre-malignant lesion which occurs and remains limited in the breast lobules. However, LCIS is a risk factor for invasive breast cancer as it can become invasive, if not treated. Both types of invasive breast carcinomas, ductal and lobular, can arise from LCIS, hence LCIS requires lifetime follow-up. LCIS forms masses of uniform, loosely cohesive cells, with no distinguishing features on gross examination. It can be identified on biopsy by two immunohistochemical (tissue) markers- E-cadherin and beta-catenin, both of which are absent in LCIS. These cells are also positive for high molecular weight keratin.

Atypical Ductal Hyperplasia (ADH) Classical Atypical hyperplasia is a pre-malignant lesion that can increase the risk of later breast cancer. It includes two types- Atypical Ductal Hyperplasia (ADH) and Atypical Lobular Hyperplasia (ALH).

ADH is a risk factor for invasive ductal carcinoma. It is similar in appearance to DCIS, but is either too small in size, or shows only partial ductal involvement to be diagnosed as DCIS. ALH is a similar condition which differs from ADH in the location of the hyperplasia, occuring in the lobules instead of the ducts. It is also a risk factor for the

Flat Epithelial Atypia (FEA) FEA is benign tumor and is generally considered as a type of atypical or high-risk lesion. However, it conveys no known risk of development further into a cancer.

Ductal Carcinoma In Situ (DCIS) DCIS is a type of pre-invasive cancer. DCIS arises from epithelial cells but remain limited to the ducts or lobules. Similar to LCIS, they have tendencies to develop into malignant carcinoma and is a significant risk factor for malignant development through a process known as lobular cancerization.

DCIS is further classified into 5 subtypes based on architectural features:
- Comedo
- Solid
- Cribriform
- Papillary
- Micropapillary
The natural history of DCIS is dependent on its grade and type. Hence DCIS can also be classified as low grade, intermediate grade and high grade DCIS. All three grades have different morphological features that assist in their diagnosis.

What are the types of Breast Carcinomas?
Invasive Breast Cancers-Malignant Cancers Invasive breast cancers are cancer cells that spread outside the lobules and ducts, growing into the stromal tissue. Invasive carcinomas have the potential to spread to other sites of body, such as the lymph nodes or other organs to form metastases. Invasive breast cancers are therefore considered as malignant breast cancers.
Invasive Ductal Carcinoma (IDC) IDC is the most common type of breast cancer, constituting about 80% of all breast cancers. IDC can occur in the presence or absence of DCIS. IDC can be classified according to the cell type, amount, type and location of secretion, architectural features and immunohistochemical profile. However, majority of IDCs fail to exhibit sufficient morphological features and are called as IDC Not Otherwise Specified (NOS/NST).

IDC subtypes include:
- IDC No Specific Type (NST)
- Tubular carcinoma
- Invasive cribriform carcinoma
- Mucinous carcinoma
- Medullary carcinoma
- Invasive papillary carcinoma
- Invasive micropapillary carcinoma
- Apocrine carcinoma
- Neuroendocrine tumor
- Metaplastic carcinoma

Invasive Lobular Carcinoma (ILC) Accounting for 10% to 15% of breast cancers, ILC begins in the milk lobules and spreads to other regions of the body. It is the second most common type of breast cancer, and occurs more commonly in older women. The incidence of ILC is reported to be increasing, particularly in postmenopausal women. ILC have different features as compared to IDC and thus differentiating between the two is important during diagnosis to predict the prognosis. ILC can also be further classified as:
- Classic type
- Histiocytoid carcinoma
- Signet ring carcinoma
- Tubulolobular carcinoma

What are Other Rare Types of Breast Cancers?
' Inflammatory Breast Cancer- A rare but fast growing cancer, the name inflammatory comes from the fact that these cancers cause the appearance of inflamed breasts (red and warm) with dimples and thick ridges. These are usually diagnosed at a younger age and are symptomized of by a rapid increase in breast size, sensations of heaviness, burning, or tenderness in the breast, or a nipple that is inverted (facing inward).
Paget's Disease of the Breast- This form of breast cancer begins in the milk ducts and spreads to the skin of the nipple and areola. Symptoms include scaliness, redness, itchiness, and irritation of the skin of nipple and areola .
Phyllodes Tumor- A very rare kind of breast cancer, phyllodes tumors can be either benign or malignant. These develop in the connective tissues of the breast and can be treated by surgical removal. It can appear at any age although the majority occur between the ages of 35 to 54 years.

What staging system is used for breast cancer?
Staging of breast cancer is essential at the time of diagnosis not only to predict its prognosis but also to help in the decision of therapy selection.
Stage 0 In this stage, the cancer is considered as carcinoma in situ as the tumor has not spread beyond the duct or lobule where it originated
Stage l The tumor is less than 2 cm in diameter and has not spread beyond the breast tissue.
Stage IIA The tumor is less than 2 cm. In addition, it has spread only to one lymph node in the armpit or to the lymph node near the breastbone on the same side as the tumor, or both.
OR The tumor is between 2 cm to 5 cm in size without spreading outside the breast.
Stage IIB The tumor is between 2 cm to 5 cm in size. In addition, it has spread only to one lymph node in the armpit, or to the lymph node near the breastbone on the same side as the tumor, or both
OR The tumor is larger than 5 cm in size without spreading outside the breast.
Stage IIIA The tumor is 5 cm or less than 5 cm in diameter. In addition, it has spread to 4.9 lymph nodes in the armpit, or has enlarged at least one lymph node near the breastbone on the same side as the tumor, or both.
OR the tumor is bigger than 5 cm and has spread to either 9 lymph nodes on the armpit as well as lymph nodes on the breastbone.
Stage IIIB The tumor has spread to the chest wall or skin or has caused inflammatory breast cancer.
Stage IIIC The tumor can be of any size, but, it has spread to 10 or more lymph nodes in the armpit, or, it has spread to lymph nodes near the collarbone, or it has spread to the lymph nodes of the armpit and enlarged at least one lymph node near the breast bone (to the same size as the tumor). It has not spread to any other parts of the body.
Stage IV Considered as metastatic breast cancer, the tumor has spread to distant parts of the body such as lungs or bones. It can be of any size.

How are breast carcinomas diagnosed?
There are several diagnostic modalities available to patients following clinical examination. These include:
- Diagnostic mammography
- Breast ultrasound
- Core needle biopsy and vacuum-assisted biopsy
- Contrast-enhanced MRI
- Galactography
- Fine-needle aspiration cytology
These are procedures can be combined with tissue examination on samples obtained by biopsy prior to surgery. The findings of tissue examination can reveal the presence or absence of estrogen and progesterone receptors, HER2 status (human epidermal growth factor receptor 2), while also assisting grading of the tumor and targeted surgical planning. Neoadjuvant systemic therapy (chemotherapy before surgery) can also be conducted where necessary. In cases of metastasis to lung, bone or liver, Computed Tomography (PET-CT Scan) of the chest or abdomen and bone scintigraphy are replacing previous staging techniques using chest X-ray and abdominal ultrasound, due to their higher sensitivity and specificity.

What is the most effective treatment for breast cancer?
- Adjuvant Drug Therapy - Adjuvant therapy is a therapy that is given along with the primary treatment to increase its effectiveness. The selection of adjuvant treatment depends upon two factors; the sensitivity of the tumor to that particular drug treatment, and the risk of relapse. This selection also takes into consideration the patient's age and other health conditions present at the time. Estimating the response of the tumor to treatment can be done by identifying its phenotypes (presence or absence of ER, PR and HER2 receptors). Endocrine therapy is a type of adjuvant therapy with the purpose of balancing or blocking hormones and can be given to most patients who have tumors that exhibit ER and/or PR. For cancers without these receptors like triple negative breast cancer, chemotherapy is more effective.
- Surgery Most cases of breast cancer today can be treated with breast conservation surgery. The surgery usually follows neoadjuvant therapy to shrink the tumor before the operation. Chemotherapy is also done following surgery to eliminate any cancer cells in the body for minimizing the risk of metastasis.
- Radiotherapy Similar to chemotherapy, radiation therapy is done to destroy cancer cells in order to reduce the chances of