Editing Breast cancer (section)

=== Classification ===
{{Main|Breast cancer classification}}

Breast cancers are classified by several grading systems, each of which assesses a tumor characteristic that impacts a person's prognosis. First, a tumor is classified by the tissue it arises from, or the appearance of the tumor tissue under a microscope. Most breast cancers (85%) are ductal carcinoma – derived from the lining of the [[mammary ducts]]. 10% are lobular carcinoma – derived from the [[Mammary gland#Structure|mammary lobes]] – or mixed ductal/lobular carcinoma.{{sfn|Hayes|Lippman|2022|loc="Invasive Breast Cancers"}} Rarer types include [[Mucinous neoplasm|mucinous carcinoma]] (around 2.5% of cases; surrounded by [[mucin]]), [[tubular carcinoma]] (1.5%; full of small tubes of [[epithelial cell]]s), [[medullary breast carcinoma|medullary carcinoma]] (1%; resembling "medullary" or middle-layer tissue), and [[Papillary carcinomas of the breast|papillary carcinoma]] (1%; covered in finger-like growths).{{sfn|Hayes|Lippman|2022|loc="Invasive Breast Cancers"}} Oftentimes a biopsy reveals cells that are cancerous but have not yet spread beyond their original location. This condition, called [[carcinoma in situ]], is often considered "precancerous" rather than a dangerous cancer itself.{{sfn|Hayes|Lippman|2022|loc="Noninvasive Breast Neoplasms"}} Those with [[ductal carcinoma in situ]] (in the mammary ducts) are at increased risk for developing true invasive breast cancer – around a third develop breast cancer within five years.{{sfn|Hayes|Lippman|2022|loc="Noninvasive Breast Neoplasms"}} [[Lobular carcinoma in situ]] (in the mammary lobes) rarely causes a noticeable lump, and is often found incidentally during a biopsy for another reason. It is commonly spread throughout both breasts. Those with lobular carcinoma in situ also have an increased risk of developing breast cancer – around 1% develop breast cancer each year. However, their risk of dying of breast cancer is no higher than the rest of the population.{{sfn|Hayes|Lippman|2022|loc="Noninvasive Breast Neoplasms"}}

Invasive tumor tissue is assigned a [[Grading (tumors)|grade]] based on how distinct it appears from healthy breast.<ref name=ACS-Grade>{{cite web|url=https://www.cancer.org/cancer/types/breast-cancer/understanding-a-breast-cancer-diagnosis/breast-cancer-grades.html |accessdate=13 February 2024 |publisher=American Caner Society |title=Breast Cancer Grade |date=8 November 2021}}</ref> Breast tumors are graded on three features: the proportion of cancer cells that form tubules, the appearance of the [[cell nucleus]], and how many cells are actively replicating.{{sfn|Harbeck|Penault-Llorca|Cortes|Gnant|2019|loc="Histologic Grade"}} Each feature is scored on a three-point scale, with a higher score indicating less healthy looking tissue. A grade is assigned based on the sum of the three scores. Combined scores of 3, 4, or 5 represent grade 1, a slower-growing cancer. Scores of 6 or 7 represent grade 2. Scores of 8 or 9 represent grade 3, a faster-growing, more aggressive cancer.<ref name=ACS-Grade/>

In addition to grading, tumor biopsy samples are tested by [[immunohistochemistry]] to determine if the tissue contains the proteins [[estrogen receptor]] (ER), [[progesterone receptor]] (PR), or [[human epidermal growth factor receptor 2]] (HER2).{{sfn|Harbeck|Penault-Llorca|Cortes|Gnant|2019|loc="Theranostic Biomarkers"}} Tumors containing either ER or PR are called "hormone receptor-positive" and can be treated with hormone therapies.<ref name=ACS-HRs>{{cite web|url=https://www.cancer.org/cancer/types/breast-cancer/understanding-a-breast-cancer-diagnosis/breast-cancer-hormone-receptor-status.html |accessdate=20 February 2024 |title=Breast Cancer Hormone Receptor Status |publisher=American Cancer Society |date=8 November 2021}}</ref> Around 15 to 20% of tumors contain HER2; these can be treated with HER2-targeted therapies.<ref>{{cite web|url=https://www.cancer.org/cancer/types/breast-cancer/understanding-a-breast-cancer-diagnosis/breast-cancer-her2-status.html |accessdate=20 February 2024 |title=Breast Cancer HER2 Status |publisher=American Cancer Society |date=25 August 2022}}</ref> The remainder that do not contain ER, PR, or HER2 are called "triple-negative" tumors, and tend to grow more quickly than other breast cancer types.<ref name=ACS-HRs/>

After the tumor is evaluated, the breast cancer case is staged using the [[American Joint Committee on Cancer]] and [[Union for International Cancer Control]]'s [[TNM staging system]].{{sfn|Harbeck|Penault-Llorca|Cortes|Gnant|2019|loc="Lymph node status and pathological stage"}} Scores are assigned based on characteristics of the tumor (T), [[lymph node]]s (N), and any metastases (M).{{sfn|AJCC Staging Manual|2017|loc="Rules for Classification"}} T scores are determine by the size and extent of the tumor. Tumors less than 2&nbsp;[[centimeter]]s (cm) across are designated T1. Tumors 2–5&nbsp;cm across are T2. A tumor greater than 5&nbsp;cm across is T3. Tumors that extend to the chest wall or to the skin are designated T4.{{sfn|AJCC Staging Manual|2017|loc="Primary Tumor (T)"}} N scores are based on whether the cancer has spread to nearby lymph nodes. N0 indicates no spread to the lymph nodes. N1 is for tumors that have spread to the closest [[axillary lymph node]]s (called "level I" and "level II" axillary lymph nodes, in the armpit). N2 is for spread to the [[intramammary lymph nodes]] (on the other side of the breast, near the chest center), or for axillary lymph nodes that appear attached to each other or to the tissue around them (a sign of more severely affected tissue).{{sfn|AJCC Staging Manual|2017|loc="Regional Lymph Nodes – Clinical"}} N3 designates tumors that have spread to the highest axillary lymph nodes (called "level 3" axillary lymph nodes, above the armpit near the shoulder), to the [[supraclavicular lymph nodes]] (along the neck), or to both the axillary and intramammary lymph nodes.{{sfn|AJCC Staging Manual|2017|loc="Regional Lymph Nodes – Clinical"}} The M score is binary: M0 indicates no evidence metastases; M1 indicates metastases have been detected.{{sfn|AJCC Staging Manual|2017|loc="Distant Metastasis (M)"}}

TNM scores are then combined with tumor grades and ER/PR/HER2 status to calculate a cancer case's "prognostic stage group". Stage groups range from I (best [[prognosis]]) to IV (worst prognosis), with groups I, II, and III further divided into subgroups IA, IB, IIA, IIB, IIIA, IIIB, and IIIC. In general, tumors of higher T and N scores and higher grades are assigned higher stage groups. Tumors that are ER, PR, and HER2 positive are slightly lower stage group than those that are negative. Tumors that have metastasized are stage IV, regardless of the other scored characteristics.{{sfn|AJCC Staging Manual|2017|loc="AJCC Prognostic Stage Groups"}}

<gallery>
File:Diagram showing stage T1 breast cancer CRUK 244.svg|Stage T1 breast cancer
File:Diagram showing stage T2 breast cancer CRUK 252.svg|Stage T2 breast cancer
File:Diagram showing stage T3 breast cancer CRUK 259.svg|Stage T3 breast cancer
File:Stage 4 of Breast Cancer.jpg|Metastatic or stage 4 breast cancer
</gallery>