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"Medical Journeys" is a set of clinical resources reviewed by physicians, meant for the medical team as well as the patients they serve. Each episode of this journey through a disease state contains both a physician guide and a downloadable/printable patient resource. "Medical Journeys" chart a path each step of the way for physicians and patients and provide continual resources and support, as the caregiver team navigates the course of a disease.

Early-stage invasive breast cancer refers to disease that has been detected at an early point in its development and has not spread beyond the breast and nearby lymph nodes. The disease is generally divided into stage 0 and stage 1 per the American Joint Committee on Cancer () staging system.

AJCC staging was originally based on anatomy alone, using primary tumor size (T), nodal involvement (N), and the presence or absence of metastasis (M) (TNM staging). The 2017 8th edition of AJCC staging presented a new prognostic staging system for breast cancer which in addition to TNM staging also includes tumor grade and estrogen receptor (ER), progesterone receptor (PR), and HER2/neu status.

Ductal carcinoma in situ (DCIS) is often referred to as stage 0 breast cancer. In this stage, concerning cells are found in the breast duct lining, but have not invaded into the surrounding tissue. DCIS is noninvasive, but it has the potential to progress to invasive breast cancer.

Stage 1 is characterized by the presence of small tumors or cancerous cells that have begun to invade nearby breast tissue, but have not yet spread to lymph nodes outside the breast or other areas of the body. Stage 1 has :

• Stage 1A: Small primary tumor up to 2 cm in diameter, with no evidence of lymph node involvement or distant metastasis (T1, N0, M0)

• Stage 1B: Small primary tumor (<2 cm) located in breast tissue (T1, N0, M0)

Local treatment options for Stage 0, Stage 1A, and Stage 1B breast cancer include surgery to remove the tumor (usually with breast-conserving surgery or mastectomy) and may include radiation therapy (RT).

There are other types of benign but high-risk breast conditions: atypical ductal hyperplasia, atypical lobular hyperplasia (ALH), and lobular carcinoma in situ and atypical lobular hyperplasia (ALH) which increase the risk of in situ and/or invasive carcinoma in either breast.

Surgery

Early-stage breast cancers are often treated with (BCT).

A surgical lumpectomy to remove the tumor is usually followed by RT to eliminate any microscopic residual disease. Radiation is sometimes omitted in elderly patients with low-risk disease.

The sentinel lymph node, the lymph node most likely to contain metastatic disease, is identified and removed during the same procedure as the lumpectomy. An axillary lymph node dissection is typically performed if the sentinel lymph node is positive for malignancy.

Not all patients with early-stage disease are candidates for BCT. , or removal of the entire breast, is recommended if the patient has:

• Genetic mutations increasing breast cancer risk

• Multicentric disease

• Large tumor size relative to breast size

• Diffuse microcalcifications

• Extensive positive margins despite re-excisions

• Inflammatory breast cancer (IBC)

• Extensive DCIS

• Scleroderma

• Patient preference; some patients may opt for mastectomy

Radiation Therapy

Depending on the choice of surgery, pathology results and patient characteristics, post-surgical RT is often done to reduce the risk of ipsilateral breast cancer recurrence. Treatment options include whole-breast radiation therapy (WBRT), hypofractionation, and partial-breast radiation.

WBRT targets the entire breast, with additional radiation delivered to the lumpectomy bed. WBRT may also include targeting of supraclavicular, axillary, and internal mammary lymph node(s) if clinically indicated.

Hypofractionation involves RT () delivered in larger doses per session over a shorter period of time. The American Society for Radiation Oncology () recommends moderately hypofractionated HYPO-RT in breast cancer regardless of the patient's age, tumor grade, or receptor status.

Systemic Therapy

Systemic therapy is the use of medications or treatments that affect the entire body to target cancer cells.

Chemotherapy

Chemotherapy is used to inhibit cell proliferation and tumor multiplication and reduce invasion and metastasis. However, chemotherapy also impacts normal cells, leading to toxic effects. Several chemotherapy regimens are used to treat early-stage breast cancer. The choice of a chemotherapy regimen is based on a combination of factors including the patient's age, overall health, tumor characteristics, and any pre-existing medical conditions.

are classified according to their mechanism of action as alkylating agents, antimetabolites, and antimicrotubular. The introduction of such as Oncotype DX and MammaPrint has revolutionized treatment decisions by helping clinicians predict the likelihood of recurrence and the potential benefits of chemotherapy.

Endocrine Therapy

Endocrine therapy is a type of treatment used for hormone receptor-positive early-stage breast cancer. Options for endocrine therapy include the selective estrogen receptor modulator tamoxifen, and aromatase inhibitors. Tamoxifen works by attaching to estrogen receptors on cancer cells, blocking estrogen from binding to these receptors and preventing the estrogen-driven growth of cancer cells.

(AIs), such as letrozole, anastrozole, and exemestane, inhibit the enzyme aromatase, which converts androgens into estrogens, decreasing estrogen production. AIs are only effective in postmenopausal women, however, as the agents do not impact ovarian estrogen production.

, such as goserelin and leuprolide, shut down hormone production in the ovaries in premenopausal women and create temporary menopause. GnRH agonists are often used in combination with tamoxifen or AIs in premenopausal patients with hormone-receptor positive breast cancer, who are at higher risk of recurrence.

Anti-HER2 Therapy

Patients with HER2-positive breast cancer will receive anti-HER2 therapy with trastuzumab (Herceptin) alone or trastuzumab plus pertuzumab (Perjeta). Trastuzumab and pertuzumab are monoclonal antibodies that target the HER2 protein, and are used in combination with chemotherapy in the neoadjuvant and/or adjuvant setting followed by maintenance anti-HER2 therapy to complete a year of treatment.

Immunotherapy

aims to stimulate the body's immune system to recognize and attack cancer cells. At this time, outside of a clinical trial, immunotherapy use for early-stage breast cancer is limited to stage II or III triple-negative breast cancer. The currently approved immunotherapy for early-stage breast cancer is pembrolizumab (Keytruda), which is a checkpoint inhibitor.

Checkpoint inhibitors are designed to block certain proteins on the surface of cancer cells or immune cells, which then allows the immune system to recognize and attack cancer cells.

Inflammatory Breast Cancer (IBC)

IBC is a form of breast cancer that typically has a rapid onset and has a distinctive presentation: the breast often appears red, swollen, and inflamed, similar to an infection or inflammation.IBC is characterized by the following:

• Rapid onset of breast erythema, edema, , and/or warm breast, with or without an underlying palpable mass

• Duration of history no more than 6 months

• Erythema occupying at least one-third of the breast

• Pathologic confirmation of invasive carcinoma

Diagnosis involves a combination of clinical examination, imaging (such as mammography, ultrasound, and MRI), and biopsy to confirm the presence of cancer cells.

Treatment typically involves a multimodal approach, including chemotherapy, mastectomy, RT, and targeted therapies, depending on tumor characteristics, including ER, PR, and HER2 status Due to the aggressive nature of IBC, a combination of treatments is often recommended.

Controversies

Early-stage breast cancer management has seen its share of controversies due to evolving scientific understanding, changes in treatment approaches, and varying opinions among healthcare professionals.

Potential concerns in early-stage disease include the following:

• : Balancing the need for aggressive treatment to prevent recurrence with potential overtreatment and its associated side effects is a significant controversy. Some argue that certain cases of early-stage breast cancer might not require intensive treatments like chemotherapy, while others advocate for a more aggressive approach to ensure the best possible outcomes.

• Axillary lymph node dissection vs sentinel lymph node biopsy (): There has been ongoing debate about the extent of lymph node surgery in early-stage disease. ALND, or removal of a substantial number of lymph nodes from the underarm area, was once more common. SLNB, a less invasive procedure to assess lymph node involvement, has a lower risk of complications. The controversy lies in deciding the best approach based on individual patient characteristics.

• : Post-lumpectomy RT can reduce the risk of local recurrence, but some research has suggested that it may be safely omitted in in certain low-risk cases. Balancing the benefits of RT against potential long-term toxic effects requires consideration of all the factors involved.

• : Hormone receptor-positive breast cancers often require hormone therapy to reduce the risk of recurrence. The optimal duration of hormone therapy is typically 5-10 years, with shorter durations potentially reducing side effects, but longer durations potentially offering better protection against recurrence.

Read previous installments in this series:

Part 1: Breast Cancer -- The Basics of Diagnosis, Staging, and Treatment

Part 2: Breast Cancer: Making the Diagnosis With Breast Biopsy