Breast cancer is a major health concern among females due to its high mortality and morbidity rate. Even with adjuvant chemotherapy, the five-year survival rate for metastatic breast cancer is less than 30%. Breast cancer incidence is higher in high-income countries than in low-income countries (571/100,000 vs. 95/10,000). Breast cancer is sometimes referred to as a collection of diseases (>100) due to the existence of numerous subtypes, including:

• Ductal carcinoma: This is the most prevalent type of breast cancer with two subtypes

o   Ductal carcinoma in situ

o   Invasive or infiltrating ductal carcinoma

• Invasive lobular carcinoma.

• Receptor-positive (Luminal A, Luminal B, Normal like, and Human epidermal growth factor receptor (HER)2-positive

• Receptor-negative (Triple negative breast cancer or Basal-like)

In the glandular tissue of the breast, breast cancer grows in the epithelial lining of the ducts (85%) or lobules (15%). The first site of the malignant development is the duct or lobule, where it typically shows a few symptoms and provides less risk of spreading (metastasis). These stage 0 tumors may develop gradually over time, invading the surrounding breast tissue, and then spreading to the nearby lymph nodes or other organs.

Breast cancer is the most common cancer diagnosed in women and forms in the cells of the breasts.

Symptoms

Different people will experience distinct breast cancer symptoms. Some people completely lack any symptoms or warning indications. Potential breast cancer symptoms include:

• New lump or mass in the breast or underarm

• Thickening or swelling of all or part of the breast (even if no lump is felt)

• Dimpling or irritated breast skin (sometimes looking like an orange peel)

• Pain in the breast or nipple area

• Dry skin or redness in the breast or nipple area

• Nipple retraction (turning inward)

• Nipple discharge (other than breast milk)

• Any change in the size or the shape of the breast

Diagnosis

Breast cancer can be detected using a variety of tests. When selecting a diagnostic test, parameters including age, general health, the type of cancer suspected, signs, and symptoms are taken into account. The tests listed below may be used to diagnose breast cancer or as follow-up for evaluation after diagnosis.

Imaging tests:

• Diagnostic mammography

• Ultrasonography

• Computed tomography (CT)

• Magnetic resonance imaging (MRI)

Biopsy:

Fine needle aspiration biopsy, core needle biopsy, surgical biopsy, image-guided biopsy, and sentinel lymph node biopsy. 

Genomic tests to predict recurrence risk:

• Oncotype DX (clinical 21 gene qRT-PCR based assay)

• MammaPrint (microarray-based gene expression profiling assay)

• EndoPredict (uses information from 12 genes to estimate the risk),

• PAM50 assay (50 gene expression assay based on microarray and quantitative real-time (qRT)-PCR). 

Additional tests:

• Ki-67 index: is an indicator of how quickly the tumor cells are multiplying. 

• Immunohistochemistry 4 (IHC): uses ER, PR, and HER2 status as well as the Ki-67 index from a sample of the tumor to estimate the risk of cancer coming back within 10 years after diagnosis.

• Breast Cancer Index (BCI, uses information from 11 genes to estimate the risk of cancer recurrence within 5 to 10 years after a diagnosis)

• Clinical Treatment Score post-5 years (CTS5, is an online tool used to predict cancer recurrence between 5 and 10 years after a diagnosis). 

Blood tests:

• Complete blood count, blood chemistry (liver and kidney function tests), and hepatitis tests (hepatitis B and/or hepatitis C). 

Further advanced imaging tests like Positron emission tomography (PET) and Single-photon emission computed tomography (SPECT) may be advised based on the stage of the tumor and the tumor biomarkers.

Management

There are numerous treatment options available for breast cancer. When breast cancer is detected early, treatment can be extremely successful, with a survival probability of 90% or greater. Often, treatment entails:

1. Surgery

To control the disease in the breast, lymph nodes, and adjacent tissues (locoregional control), surgery is performed. In the past, mastectomy (complete removal of the breast) was the only surgical procedure used to treat breast cancer. Mastectomy may still be required for large tumors. Most breast cancers can now be treated with a less invasive procedure called a "lumpectomy" or partial mastectomy, in which only the tumor is removed from the breast.

2. Radiation therapy

Radiotherapy is crucial in the management of breast cancer. Moreover, radiation therapy can postpone mastectomy in cases of early-stage breast cancer. Even after a mastectomy, radiotherapy may lower the chance of cancer recurrence in patients with advanced malignancies.

3. Chemotherapy

The majority of chemotherapy regimens may be advised as neoadjuvant (before surgery) or adjuvant (after surgery). Common chemotherapeutic drugs include Docetaxel (Taxotere), Paclitaxel (Taxol), Doxorubicin (generic drug), Epirubicin (Ellence), Capecitabine (Xeloda), Carboplatin (generic drug), Cyclophosphamide (generic drug), Fluorouracil (5-FU), Methotrexate (Rheumatrex, Trexall), and Protein-bound paclitaxel (Abraxane).

4. Anti-HER2 treatments

Anti-HER2 treatments are recommended in either neoadjuvant or adjuvant cancer therapies. Common anti-HER2 therapeutics include Trastuzumab, Pertuzumab, Neratinib, Ado-trastuzumab emtansine or T-DM1, and a combination of Pertuzumab, trastuzumab, and hyaluronidase.

5. Endocrine therapy

After surgery, endocrine therapy (tamoxifen, aromatase inhibitors, ovarian ablation/suppression) is typically advised; however, women at low risk of recurrence may get neoadjuvant delivery. Neoadjuvant endocrine therapy with an aromatase inhibitor may be recommended for postmenopausal patients with HR-positive/HER2-negative disease to improve locoregional therapeutic control.

6. Bone modifying drugs

Bone-modifying drugs prevent bone deterioration and strengthen the bone. They can be used to treat cancer that has spread to the bone or to stop it from recurring and they consist of:

o   Bisphosphonates, block the osteoclasts or bone-destroying cells.

o   Denosumab, an osteoclast-targeted therapy.

7. Immunotherapy

Immunotherapy strengthens the immune system's ability to attack cancer cells to combat the disease. Immune checkpoint inhibitors are prescribed for the treatment of triple-negative, early-stage, high-risk breast cancer. Pembrolizumab, an immune checkpoint inhibitor, has been approved by the FDA for use in combination with chemotherapy. 

A revolutionary change from a one-size-fits-all approach to personalized medicine is occurring in the diagnosis and treatment of breast cancer. A better understanding of the tumor can be achieved with the help of sophisticated diagnostics, such as molecular imaging and genomic expression profiles. A coordinated multidisciplinary strategy to minimize recurrence and reduce treatment-associated morbidity is produced by these diagnostics in combination with more modern surgical procedures and radiation therapies.