Breast cancer type can be classified in many ways such as where it originates, the extent of spread, tumor stage, tumor grade, and molecular subtype. Tumor staging describes the size of the tumor and its’ spread and ranges from 0 to IV with 0 being the least severe and 4 being the most severe. Stage 0 tumors possess either cancer cells or abnormal noncancerous cells that have not spread to tissues outside of their origin, while Stage IV cancers have spread to distant parts of the body.[1] Tumor grade refers to how abnormal the cancer cells look with low grade meaning the cancer cells look similar to normal cells and high grade meaning the cancer cells look very different.[2]

When classifying by extent of spread, there are two main options: in situ and invasive. Ductal carcinoma in situ (DCIS) is breast cancer that originates in the milk duct and has not spread to the surrounding breast tissue, therefore being classified as non-invasive.[3] DCIS makes up roughly 20% of all breast cancers. DCIS is also referred to as intraductal carcinoma or Stage 0 breast cancer. DCIS cannot metastasize since it has not spread to the surrounding tissue, but it can progress into becoming an invasive breast cancer.[4] Contrarily, invasive breast cancer is characterized by its spread to the surrounding tissue. Invasive breast cancer can be further divided into subtypes based on where the tumor originated, with the two most common subtypes being invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC).[1] IDC is the most common type of breast cancer, constituting 70-80% of all breast cancers while ILC makes up about 10% of cases.3,5 IDC originates in the milk duct whereas ILC originates in the milk-producing lobules.[5]

Important terms to understand when classifying breast cancer types are HER2 (human epidermal growth factor receptor 2) status and hormone status. HER2, a protein encoded by the HER2 gene, promotes growth; therefore, breast cancers with an excess of this protein tend to grow and spread quickly. Estrogen and progesterone are hormones that can increase cancer growth if the tumor has receptors for them. When the breast tumor has hormone receptors, the hormones in the body can bind to these receptors and promote cancer cell growth.[6]

Other types of invasive breast cancer are triple-negative breast cancer (TNBC) and inflammatory breast cancer (IBC).[3] TNBC may also be referred to as basal-like when classifying by molecular subtype. TNBC is characterized by not having estrogen and progesterone hormone receptors, while also not producing excessive amounts of HER2 protein. TNBC constitutes 10-15% of all breast cancers and is the most common type of cancer for women with the BRCA1 (breast cancer 1) mutation, the most frequent inherited gene that causes breast cancer. TNBC is considered a more aggressive type of breast cancer due to its quick growth and limited treatment options due to the inability to utilize specific therapies such as targeting hormone receptors or HER2.[7]

IBC is more uncommon than TNBC, making up only ~1-5% of all breast cancers.3 IBC is often a subtype of IDC, but has different symptoms of inflammation such as excessive redness, swelling, and dimpling or thickening of the skin of the breast caused by the cancer cells blocking lymph vessels in the skin. Because IBC is defined as having the cancer cells spread to the skin, it is always at least Stage 3 at the time of diagnosis. IBC is considered an aggressive type of breast cancer, and outlook is worse than for other types of breast cancers because of its quick growth, and the cancer will often have metastasized by the time of diagnosis (roughly in a third of all diagnosed cases). IBC is also more common in overweight women since having more adipose or fat tissue increases inflammation and estrogen levels which can increase the risk of developing breast cancer.8 Both TNBC and IBC are more common in women under 40 years old and African American women because these more aggressive types of breast cancer often result from a genetic predisposition.[7,8]

When classifying breast cancers by molecular subtype, there are 5 common subtypes: luminal A, luminal B, TNBC, HER2-enriched, and normal-like. Luminal A describes breast tumors that are hormone receptor positive, HER2 negative, low grade, and have low Ki-67 levels[MB1] .[9] Ki-67 is a protein present in proliferating cancer cells; therefore, the amount of the protein present is used as an indicator for how aggressive the cancer is.[10] Luminal B breast tumors are hormone receptor positive, HER2 positive or HER2 negative with high Ki-67 levels and tend to grow faster than luminal A cancers. TNBC has been discussed previously and describes breast tumors that are hormone receptor negative and HER2 negative. HER2-enriched tumors are hormone receptor negative and HER2 positive. This type of cancer tends to grow faster than the luminal types but can be treated using specific therapies that target HER2. Normal-like breast tumors are very similar to luminal A cancers (hormone receptor positive, HER2 negative, low Ki-67 levels) but tend to have a slightly worse prognosis than luminal A cancers.[9]

There are rare types of breast cancer that originate in cells of the breast other than the milk ducts or lobules: angiosarcoma, Paget disease of the breast, and phyllodes tumor.[3] Angiosarcoma makes up less than 1% of all breast cancers and originates in the blood or lymphatic vessels of the breast. The most common cause of angiosarcoma is a complication from previous radiation therapy. This type of breast cancer tends to grow and spread quickly.[11] Paget disease of the breast makes up 1-3% of all breast cancer cases.3 It affects the skin of the nipple and areola and typically only affects one breast. In 80-90% of cases, Paget disease is found alongside DCIS or IDC.[12] Phyllodes tumors of the breast make up less than 1% of all breast tumors.[13] These tumors originate in the connective tissue of the breast, and 1 out of 4 are cancerous. Phyllodes tumors are most common in women in their 40s, and women with the rare inherited disorder Li-Fraumeni syndrome are at an increased risk.[14]

 [MB1]Link to ‘breast cancer ploidy and cell proliferation’ article

References

1.     Breast Cancer Stages: 0 Through IV https://www.breastcancer.org/symptoms/diagnosis/staging (accessed Apr 30, 2021).  

2.     Tumor Grade Fact Sheet https://www.cancer.gov/about-cancer/diagnosis-staging/prognosis/tumor-grade-fact-sheet (accessed Apr 30, 2021).

3.     Types of Breast Cancer: Different Breast Cancer Types https://www.cancer.org/cancer/breast-cancer/understanding-a-breast-cancer-diagnosis/types-of-breast-cancer.html (accessed Apr 27, 2021).

4.     Ductal Carcinoma in Situ (DCIS) https://www.cancer.org/cancer/breast-cancer/understanding-a-breast-cancer-diagnosis/types-of-breast-cancer/dcis.html (accessed Apr 27, 2021).

5.     Invasive Breast Cancer (IDC/ILC): Types of Invasive Breast Carcinoma https://www.cancer.org/cancer/breast-cancer/understanding-a-breast-cancer-diagnosis/types-of-breast-cancer/invasive-breast-cancer.html (accessed Apr 27, 2021).

6.     Types of Breast Cancer: Triple Negative, ER-Positive, HER2-Positive https://www.webmd.com/breast-cancer/breast-cancer-types-er-positive-her2-positive (accessed Apr 30, 2021).  

7.     Triple-negative Breast Cancer: Details, Diagnosis, and Signs https://www.cancer.org/cancer/breast-cancer/understanding-a-breast-cancer-diagnosis/types-of-breast-cancer/triple-negative.html (accessed Apr 27, 2021).

8.     Inflammatory Breast Cancer: Details, Diagnosis, and Signs https://www.cancer.org/cancer/breast-cancer/understanding-a-breast-cancer-diagnosis/types-of-breast-cancer/inflammatory-breast-cancer.html (accessed Apr 27, 2021).

9.     Molecular subtypes of breast cancer https://www.breastcancer.org/symptoms/types/molecular-subtypes (accessed Apr 27, 2021).

10.  Stephan, P. How and Why the Ki-67 Test Is Used in Breast Cancer Treatment https://www.verywellhealth.com/ki-67-tumor-marker-test-430609 (accessed Apr 27, 2021).

11.  Angiosarcoma of the Breast: Breast Angiosarcoma https://www.cancer.org/cancer/breast-cancer/understanding-a-breast-cancer-diagnosis/types-of-breast-cancer/angiosarcoma-of-the-breast.html (accessed Apr 30, 2021).

12.  Paget Disease of the Breast: Nipple Cancer https://www.cancer.org/cancer/breast-cancer/understanding-a-breast-cancer-diagnosis/types-of-breast-cancer/paget-disease-of-the-nipple.html (accessed Apr 30, 2021).

13.  Phyllodes Tumors of the Breast: Overview and Treatment https://www.breastcancer.org/symptoms/types/phyllodes#:~:text=Phyllodes%20tumors%20of%20the%20breast%20are%20rare%2C%20accounting,these%20tumors%20are%20phylloides%20tumor%20and%20cystosarcoma%20phyllodes. (accessed Apr 30, 2021).

14.  Phyllodes Tumors of the Breast https://www.cancer.org/cancer/breast-cancer/non-cancerous-breast-conditions/phyllodes-tumors-of-the-breast.html (accessed Apr 30, 2021).