Stages and grades of breast cancer

When you are diagnosed with breast cancer, the first step is to find out the tumor’s size, if it has invaded neighboring tissues, and whether it has spread to other body areas. This process is referred to as breast cancer staging¹.

Breast cancer staging involves two main methods: anatomic and prognostic. Anatomical staging assesses tumor size, lymph nodes, and distant metastasis, while prognostic includes tumor grade and biomarkers.

There are different methods the physicians and healthcare providers use to find out the breast cancer stages. These include physical examinations, biopsies², and imaging techniques such as mammograms, ultrasound, MRI, bone scans, CT scans and PET scans.

In breast cancer staging, your physician will also take into consideration what is called the TNM scale. T represents the tumor size, N describes lymph node involvement, and M represents the metastatic state of the cancer cells, that is, whether it has spread to other parts of the body.

Using the information acquired during staging, healthcare professionals can determine the best course of action, whether it entails surgery, chemotherapy, radiation therapy, or a combination of treatments.

There are several stages of breast cancer, characterized by the progression of the disease.

Stage 0 breast cancer, also known as Carcinoma in Situ, refers to a very early form of breast cancer where cancerous cells are located in the walls of a breast duct or lobe but have not invaded nearby tissues.

It is often considered non-invasive, as the abnormal cells are confined within the duct and have not spread to surrounding areas. The two main types of stage 0 breast cancer are composed of Ductal Carcinoma in Situ (DCIS) and Lobular Carcinoma in Situ (LCIS).

Treatment options for Stage 0 breast cancer

At Stage 0, there are several primary treatment options:

• Lumpectomy or mastectomy

A lumpectomy³ can be performed, where the lump is removed without axillary assessment together with radiotherapy. A mastectomy can also be performed, in which the whole affected breast is removed.

• Monitoring

The patient can undergo intermittent monitoring, with the help of mammography.

• Medication

The patient can undergo hormone therapy if the cancer is hormone receptor positive or targeted therapy if the cancer is HER2+.

• Radiation Therapy

Radiation is often used after surgery to help prevent the cancer from coming back.

Early-stage breast cancer is divided into Stages I and II.

Stage I breast cancer

Stage I breast cancer is divided into IA and IB.

At IA, the tumor is contained within the breast and is no more than 2 cm in size.

At IB, the tumor is 2 cm or smaller, or there is no tumor in the breast but small clusters of cancer cells > 0.2mm but < 2mm are found in the lymph nodes.

Treatment options for Stage I breast cancer

Treatment for Stage I breast cancer involves a combination of local and systemic therapies, which aim to eliminate cancer cells and prevent recurrence. Common treatment modalities include:

Lumpectomy or Mastectomy

A lumpectomy is the removal of the tumor, and a tiny portion of the surrounding healthy tissue is removed. This is often followed by radiation therapy.

A mastectomy involves the removal of the entire breast. In some cases, lymph node biopsy or removal may be performed to assess cancer spread.

Radiotherapy

Radiotherapy is used to target any cancer cells that may still be present in the breast after a lumpectomy.

Hormone Therapy

Hormone therapy may be advised for breast cancers that are hormone receptor-positive. Medications like tamoxifen or aromatase inhibitors may be prescribed to block hormones that fuel the growth of certain types of breast cancer cells.

Chemotherapy

In some cases, especially if there is a higher risk of recurrence, chemotherapy may be recommended. The specific drugs⁴ and regimens depend on the characteristics of the cancer.

Targeted Therapy

Targeted therapies, such as trastuzumab⁵ (Herceptin), may be considered for HER2+ breast cancers. This medication targets a specific protein (HER2) that is overexpressed in some breast cancers.

Stage II breast cancer

Stage II breast cancer is divided into IIA and IIB⁶.

At IIA, a tumor of no more than 2 cm or no tumor at all, is discovered in the breast. Three to five axillary lymph nodes may have cancer larger than 2 mm, or the tumor may be larger than 2 cm but smaller than 5 cm.

At IIB, the tumor measures more than 2 cm but not more than 5 cm. The lymph nodes contain little clusters of breast cancer cells that are bigger than 0.2 mm but not greater than 2 mm, or a tumor that is larger than 2 cm but smaller than 5 cm, with cancer that has extended to 1 – 3 axillary lymph nodes or lymph nodes around the breast bone. It may also describe a tumor that is greater than 5 cm but has not extended to the lymph nodes.

Treatment options for Stage II breast cancer

Treatment for Stage II breast cancer is comprehensive, and it includes a combination of local and systemic therapies. The treatment plan may differ based on the features of the cancer tumor, such as hormone receptor state, HER2 status, and the patient’s overall health.

Here is an overview of the treatment options for Stage II breast cancer:

Lumpectomy or Mastectomy

The choice between lumpectomy (excision of the tumor together with a tiny portion of the surrounding healthy tissue) and mastectomy (removal of the entire breast) depends on factors such as tumor size, location, and patient preference.

Sentinel Node Biopsy or Lymph Node Dissection

The surgeon may do a sentinel node biopsy if lymph node⁷ involvement is suspected, to evaluate the condition of the initial lymph nodes that the cancer cells are likely to extend to. In some cases, additional lymph nodes may be removed.

Radiation Therapy

Radiation therapy is administered after lumpectomy to target any remaining cancer cells in the breast. It may also be recommended after mastectomy in some instances.

Chemotherapy

Chemotherapy is often recommended for Stage II breast cancer, especially if the tumor is larger or if there is lymph node involvement. Chemotherapy seeks to eradicate cancer cells that have perhaps traveled outside of the breast. The specific drugs and regimen depend on the characteristics of the cancer.

Hormone Therapy

Hormone therapy may be advised for breast cancers that are hormone receptor-positive. Drugs like aromatase inhibitors and tamoxifen may be administered to suppress hormones that promote the growth of specific kinds of breast cancer cells.

Targeted Therapy

If the cancer is HER2-positive, targeted therapies such as trastuzumab (Herceptin) may specifically target HER2-positive cancer cells.

Immunotherapy

In some cases, immunotherapy may be considered to stimulate the body’s immune system to recognize and attack cancer cells.

Stage III breast cancer is often referred to Locally Advanced Breast Cancer (LABC). It is divided into IIIA, IIIB, and IIIC⁸.

At IIIA, no tumor is found, or a tumor of varying sizes with the involvement of 4 to 9 axillary lymph nodes is found. Alternatively, the tumor may be bigger than 5 cm with small clusters of breast cancer cells > 0.2 mm but < 2 mm are seen in the lymph nodes, or the tumor is more than 5 cm and has moved to 1 – 3 axillary lymph nodes.

At IIIB, tumors of any size have spread to the skin of the breast with accompanying swelling or ulcers, the chest wall, and/or lymph nodes above or below the clavicle.

IIIC is identical to stage IIIB, except the cancer has progressed to lymph nodes above or below the collarbone, lymph nodes close to the sternum, and lymph nodes in the axilla.

Treatment of Stage III breast cancer

There are several treatment modalities:

Neoadjuvant Therapy

Neoadjuvant therapy comprises the administration of systemic treatments such as hormone therapy, chemotherapy, or targeted therapy before surgery. This approach is often used in Stage III to shrink the tumor and make it more manageable for surgical removal. Neoadjuvant therapy may also help assess the response to treatment.

Chemotherapy

Administered before surgery (neoadjuvant) or after surgery (adjuvant) to target cancer cells throughout the body. The specific drugs and regimen depend on the characteristics of the cancer.

Hormone Therapy

For hormone receptor-positive tumors, hormone therapy may be a part of the treatment plan to block hormone receptors and reduce the risk of recurrence.

Targeted Therapy

If the cancer is HER2-positive, targeted therapies like trastuzumab (Herceptin) may specifically target HER2-positive cancer cells.

Radiation Therapies

Radiation therapies include External Beam Radiation, which is administered to the affected breast or chest wall to target any remaining cancer cells after surgery, and Internal Radiation (Brachytherapy), where internal radiation may be used to deliver radiation directly to the tumor site.

Mastectomy

A mastectomy⁹ is often the primary surgical intervention for Stage III breast cancer. This may involve the removal of the entire breast (simple mastectomy) or the breast and underlying chest muscles (modified radical mastectomy).

Lymph Node Dissection

Lymph node dissection involves the excision of additional lymph nodes to assess the degree of lymph node involvement.

What is MBC?

Also known as Stage IV breast cancer, Metastatic Breast Cancer (MBC) represents the most advanced phase of breast cancer associated with the spread to both nearby lymph nodes and distant regions beyond the breast. This final stage of breast cancer entails potential involvement in organs like the lungs, liver, brain, or bones¹⁰.

Metastatic breast cancer confers a poor prognosis as there is no cure.  However, treatments may improve quality of life and help patients live as long as possible. The five-year metastatic breast cancer survivorship rate is 30% for women in the US¹¹. This mean that 3 in 10 women with metastatic breast cancer are likely as women in the general population to survive for five years after diagnosis.

What is breast cancer grading?

Breast cancer grading involves assessing the characteristics of cancer cells under a microscope. It focuses on how closely they resemble normal breast tissue and how quickly they are likely to grow and spread.

Breast cancer grades are commonly grouped into three. They are:

Grade 1 (Low Grade)
At Grade 1, the cancer cells closely resemble normal breast cells. They tend to grow slowly.

The cells are well-differentiated, meaning they retain some of the features of normal cells.

Generally, it is associated with a better prognosis.

Grade 2 (Intermediate Grade)
At Grade 2, the cancer cells have some abnormal features but are not as abnormal as high-grade cancer cells. Moderate differentiation shows characteristics between well-differentiated and poorly differentiated cells. There is a moderate growth rate, and the prognosis falls between Grades 1 and 3.

Grade 3 (High Grade)
At Grade 3, the cancer cells look very different from normal cells, as they have lost many usual features. These cancer cells tend to grow more rapidly¹², resulting in a raised risk of recurrence and a worse prognosis.

The staging and grading of breast cancer are important to help determine the best management and treatment modalities and the prognosis of the cancer, respectively, about dedicated patient care.

With medical advances, better staging techniques have yielded more accurate results. It is, however, vital that patients present early to clinics to improve the prognosis of this disease. Regular breast screening is recommended for women above 50 years for early detection of breast cancer. Nevertheless, if every woman of any age is committed to breast health awareness, the incidence of metastatic breast cancer is likely to decline.

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3. “Breast Surgery & Reconstruction.” UC San Diego Health https://health.ucsd.edu/care/cancer/cancers-we-treat/breast/
4. “Chemotherapy.” Yale Medicine. https://www.yalemedicine.org/conditions/chemotherapy
5. “Herceptin.” Breast Cancer Organization. https://www.breastcancer.org/treatment/targeted-therapy/herceptin
6. “Breast Cancer Staging.” Penn Medicine. https://www.pennmedicine.org/cancer/types-of-cancer/breast-cancer/breast-cancer-staging
7. “Precision treatment for breast cancer.” Yale Medicine https://yalemedicine.org/news/precision-treatment-for-breast-cancer
8. “Stage 3 (III) A, B, And C Breast Cancer Overview.” National Breast Cancer Foundation, Inc. https://www.nationalbreastcancer.org/breast-cancer-stage-3/
9. Ibid.
10. “Metastatic Breast Cancer.” Penn Medicine: Abramson Cancer Center. https://www.pennmedicine.org/cancer/types-of-cancer/breast-cancer/types-of-breast-cancer/metastatic-breast-cancer
11. “Breast Cancer – Metastatic: Statistics.” Cancer.Net. Published February 2023. https://www.cancer.net/cancer-types/breast-cancer-metastatic/statistics#:~:text=Instead%2C%20these%20statistics%20describe%20trends,metastatic%20breast%20cancer%20is%2019%25
12. ”Cancer grades.” Cancer Research UK. https://www.cancerresearchuk.org/about-cancer/what-is-cancer/cancer-grading