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The breast is made up of several tissues, ranging from very fatty to very thick. A network of lobes exists within this tissue. Each lobe is made up of lobules, which are tiny tube-like structures that contain milk glands. The glands, lobules, and lobes are linked by tiny ducts that transport milk from the lobes to the nipple. The nipple is in the center of the areola, which is the darker area surrounding the nipple. Blood and lymph vessels travel throughout the breast as well. The cells are nourished by blood. The lymphatic system discharges body waste. The lymph vessels connect to lymph nodes, which are little bean-shaped organs that aid in infection fighting. Lymph node clusters can be found in a variety of locations throughout the body, including the neck, groin, and belly. Regional lymph nodes of the breast are those that are close to the breast, such as those under the arm.
BREAST CANCER
TYPES OF BREAST CANCER
- Ductal carcinoma in situ (DCIS): This is a non-invasive cancer that has only expanded within the duct and has not spread outside of it.
- Invasive or infiltrating ductal carcinoma: Cancer has spread outside of the duct in this case.
SUBTYPES OF BREAST CANCER
SYMPTOMS AND SIGNS OF BREAST CANCER
- A heated, red, swollen breast with or without a rash and dimpling resembling orange skin, known as “peau d’orange.”
- Pain in the breast, particularly persistent breast pain Although pain is not usually a sign of breast cancer, it should be reported to a doctor.
- A firm knot-like bulge or thickening in the breast or beneath the arm. It is critical to feel the same place in the opposite breast to ensure that the change is not a result of healthy breast tissue in that area.
- Changes in breast size or form.
- Nipple discharge that happens unexpectedly, is bloody, or affects only one breast.
- Physical changes, such as a nipple that has rotated inwards or a pain in the nipple area.
- Irritation or changes in the skin, such as puckering, dimpling, scaliness, or new wrinkles
STAGES OF BREAST CANCER
Tumor (T)
- Tis (DCIS): DCIS is a non-invasive malignancy that, if left untreated, can progress to aggressive breast cancer. DCIS indicates that cancer cells have been discovered in the breast ducts but have not spread beyond the layer of tissue where they began.
- Tis (DCIS): Paget disease of the nipple is an uncommon type of early, non-invasive cancer that solely affects the nipple’s skin cells. Paget disease is sometimes linked to invasive breast cancer. If invasive breast cancer exists, it is classed based on the stage of the invasive tumor.
- T1mi tumor is one that is one millimeter or less in size.
- T1a tumors are those that are greater than 1 mm but less than 5 mm in size.
- T1b tumors are those that are larger than 5 mm but smaller than 10 mm.
- T1c tumors are those that are larger than 10 mm but smaller than 20 mm.
- T4a indicates that the tumor has spread into the chest wall.
- T4b is the stage at which the tumor has penetrated the skin.
- T4c cancer has spread to the chest wall and the skin.
- T4d is an inflammatory form of breast cancer.
Node (N)
- The axillary lymph nodes(lymph nodes found beneath the arm).
- Above and below the collarbone lymph nodes
- Internal mammary lymph nodes(lymph nodes found behind the breastbone).
- There was no malignancy identified in the lymph nodes.
- Only cancerous spots smaller than 0.2 mm are found in the lymph nodes.
Metastasis (M)
Cancer stage grouping
- Although there is no sign of a tumor in the breast, the cancer has migrated to one to three axillary lymph nodes. It hasn’t spread to other sections of the body yet. (T0, N0, M0.)
- The tumor is 20 mm or less in diameter and has migrated to one to three axillary lymph nodes (T1, N1, M0).
- The tumor is more than 20 mm but less than 50 mm in size, and it has not migrated to the axillary lymph nodes (T2, N0, M0).
DIAGNOSIS OF BREAST CANCER
- The cancer type suspected
- Your symptoms and signs
- Your age and general well-being
- The outcomes of previous medical tests
Imaging tests
Biopsy
Examining the biopsy sample
Blood tests
- Complete blood count: A complete blood count (CBC) is a test that counts the quantity of different types of cells in a person’s blood, such as red blood cells and white blood cells. It is done to ensure that your bone marrow is working properly.
- Blood chemistry: This test determines how well your liver and kidneys are functioning.
- Hepatitis tests: While not now the standard of care, these tests are done on occasion to look for signs of prior hepatitis B and/or hepatitis C exposure. If you have active hepatitis B, you may need to take a particular drug to suppress the virus before receiving chemotherapy. Chemotherapy can cause the virus to develop and damage the liver if it is not given this medication.
Genomic tests to estimate the chance of recurrence
- Recurrence score less than 16: Hormonal therapy is routinely advised, although chemotherapy is rarely required.
- Recurrence score of 16 to 30: Chemotherapy may be prescribed prior to hormonal therapy.
- Recurrence score of 31 or higher: Chemotherapy is frequently prescribed before hormone treatment.
- Recurrence score less than 26: Hormonal therapy is routinely advised, although chemotherapy is rarely required.
- Recurrence score of 26 to 30: Chemotherapy may be prescribed prior to hormonal therapy.
- Recurrence score of 31 or higher: Chemotherapy is frequently prescribed before hormone treatment.
- PD-L1: PD-L1 is located on the surface of cancer cells as well as some immune cells in the body. This protein prevents the body’s immune cells from eliminating the cancer, which is particularly important in triple-negative breast cancer.
- Microsatellite instability-high (MSI-H) or DNA mismatch repair deficiency (dMMR): Tumors with MSI-H or dMMR have trouble repairing DNA damage. This signifies that they undergo a great deal of mutation or change. These modifications cause aberrant proteins to be produced on tumor cells, making it easier for immune cells to locate and fight the tumor.
- NTRK gene fusions: This is a specific genetic mutation that has been discovered in a variety of cancers, including breast cancer.
- PI3KCA gene mutation: This is a particular genetic alteration that is frequently discovered in breast cancer.
TREATMENT OF BREAST CANCER
- The subtype of the tumor, which includes hormone receptor status (ER, PR), HER2 status, and nodal status.
- The cancer’s stage.
- If necessary, genomic markers such as Oncotype DXTM or MammaPrintTM can be used.
- Age, general health, menopausal status, and preferences of the patient
- The existence of known mutations in breast cancer genes such as BRCA1 or BRCA2.
- Because the tumor is smaller, surgery may be less difficult.
- Your doctor may investigate whether some cancer treatments are effective.
- A clinical study may also allow you to explore a new medicine.
- If you have any microscopic distant disease, it will be addressed as soon as possible.
- If the tumor decreases enough before surgery, women who might have needed a mastectomy may be able to receive breast-conserving surgery (lumpectomy).
Surgery
Removal, analysis, and treatment of lymph nodes
- Radiation therapy is not advised if there is no sign of malignancy in the lymph nodes before or after chemotherapy.
- Radiation therapy is appropriate if there was evidence of cancer in the lymph nodes prior to chemotherapy and there is no longer evidence of cancer in the lymph nodes following chemotherapy.
- If there is evidence of malignancy in the lymph nodes following chemotherapy, an axillary lymph node dissection as well as radiation therapy are both suggested.
Reconstructive (plastic) surgery
- Many women do not find it troublesome enough to replace saline implants since they “ripple” at the top or shift with time.
- Saline implants have a different feel than silicone implants. They are frequently more firm to the touch than silicone implants.
- Transverse rectus abdominis muscle (TRAM) flap: This technique, which can be performed as a pedicle flap or a free flap, employs muscle and tissue from the lower stomach wall.
- Latissimus dorsi flap: The upper back muscle and tissue are used in this pedicle flap technique. During this flap operation, implants are frequently implanted.
- Deep inferior epigastric artery perforator (DIEP) flap: The DIEP free flap removes tissue from the abdomen, and the blood vessels are attached to the chest wall by the surgeon.
- Gluteal free flap: The gluteal free flap creates the breast using tissue and muscle from the buttocks, and the surgeon also attaches the blood arteries. Transverse upper gracilis (TUG), which utilises upper thigh tissue, may also be an option.
External breast forms (prostheses)
Radiation therapy
- External-beam radiation therapy: This is the most prevalent type of radiation treatment, and it is delivered by a machine located outside the body. This comprises full breast radiation therapy, partial breast radiation therapy, and expedited breast radiation therapy, which can be completed in a matter of days rather than weeks.
- Intra-operative radiation therapy: This is when radiation therapy is administered in the operating room with the help of a probe.
- Brachytherapy: Radiation therapy of this type is administered by inserting radioactive sources into the tumor.
Schedule for radiation therapy
- After a lumpectomy: External-beam radiation therapy is given Monday through Friday for 3 to 4 weeks after a lumpectomy if the malignancy is not in the lymph nodes. If the cancer has spread to the lymph nodes, radiation therapy is administered for 5 to 6 weeks. This duration is evolving, since there is a preference for a shorter duration in women who fit the criteria for shorter treatment. This is frequently preceded with radiation therapy to the entire breast, followed by a more concentrated treatment to the location of the tumor in the breast for the remaining sessions.
This targeted element of the treatment, known as a boost, is usual for women with invasive breast cancer to lower the likelihood of a breast recurrence. Women with DCIS may potentially benefit from the treatment. The increase may be optional for women who have a low risk of recurrence. It is critical to discuss this treatment strategy with your doctor.
- After a mastectomy: Radiation therapy is normally administered 5 days a week for 5 to 6 weeks to people who require it after a mastectomy. Radiation therapy can be administered either before or after reconstructive surgery. As with lumpectomy, some women may be advised to receive less than 5 weeks of radiation therapy after mastectomy.
- Partial breast irradiation: Partial breast irradiation (PBI) is radiation therapy that targets only the tumor area rather than the entire breast. It is more common following a lumpectomy. Directly targeting radiation to the tumor location usually reduces the amount of time patients need to receive radiation therapy. However, PBI may be available to only a subset of patients. PBI is still being explored, despite encouraging early results. However, in some cases, such as for persons with early-stage breast cancer, it is already part of standard care. You should explore the benefits and drawbacks of PBI versus whole breast radiation therapy with your radiation oncologist.
PBI can be performed using normal external-beam radiation therapy that focuses on the area where the tumor was removed rather than the entire breast. PBI can also be used with brachytherapy, with plastic catheters or a metal wand temporarily implanted in the breast. Breast brachytherapy treatment periods might range from one dosage to one week. It can also be administered as a single dose in the operating room shortly following tumor removal. These types of targeted radiation therapy are currently reserved for patients with tumors that are smaller, less aggressive, and lymph node-negative.
- Proton therapy: To kill cancer cells, standard radiation therapy for breast cancer employs x-rays, commonly known as photon therapy. Proton treatment is a type of external-beam radiation therapy in which protons are used instead of x-rays. Protons have the ability to destroy cancer cells at high energies. Because protons have different physical properties than photons, they may allow radiation therapy to be more focused and potentially minimize the radiation dose. The therapy may help lower the quantity of radiation that is delivered to the heart. In a national clinical trial, researchers are comparing the benefits of proton therapy vs photon therapy. Proton therapy is currently an experimental treatment that may not be widely available or reimbursed by health insurance.
- Intensity-modulated radiation therapy: Intensity-modulated radiation treatment (IMRT) is a more advanced method of treating the breast with external-beam radiation therapy. To better target the tumor and disperse the radiation more uniformly throughout the breast, the strength of the radiation directed at it is changed. The use of IMRT reduces the radiation dose and may reduce potential harm to surrounding organs such as the heart and lungs, as well as the risks of some immediate adverse effects such as skin peeling during treatment. This is especially crucial for women with medium to large breasts, who are more likely to experience adverse effects such as peeling and burning than women with smaller breasts. IMRT may also assist to reduce the long-term effects on breast tissue that were typical with previous radiation treatments, such as hardness, edema, or discolouration.
IMRT is not suitable for everyone. To learn more, speak with your radiation oncologist. Coverage for IMRT may also necessitate special insurance approval. It is critical to verify with your health insurance company before beginning any treatment to ensure that it is covered.
Concerns about adjuvant radiation therapy for older individuals and/or those with a tiny tumor
Chemotherapy
- Eribulin (Halaven)
- Fluorouracil (5-FU)
- Gemcitabine (Gemzar)
- Ixabepilone (Ixempra)
- Methotrexate (Rheumatrex, Trexall)
- Protein-bound paclitaxel (Abraxane)
- Vinorelbine (Navelbine)
- Docetaxel (Taxotere)
- Paclitaxel (Taxol)
- Doxorubicin (available as a generic drug)
- Epirubicin (Ellence)
- Pegylated liposomal doxorubicin (Doxil)
- Capecitabine (Xeloda)
- Carboplatin (available as a generic drug)
- Cisplatin (available as a generic drug)
- Cyclophosphamide (available as a generic drug)
- AC (doxorubicin and cyclophosphamide)
- EC (epirubicin, cyclophosphamide)
- AC or EC followed by T (paclitaxel or docetaxel), or the reverse)
- CAF (cyclophosphamide, doxorubicin, and 5-FU)
- CEF (cyclophosphamide, epirubicin, and 5-FU)
- CMF (cyclophosphamide, methotrexate, and 5-FU)
- TAC (docetaxel, doxorubicin, and cyclophosphamide)
- TC (docetaxel and cyclophosphamide)
- AC-TH (doxorubicin, cyclophosphamide, paclitaxel or docetaxel, trastuzumab)
- AC-THP (doxorubicin, cyclophosphamide, paclitaxel or docetaxel, trastuzumab, pertuzumab)
- TCH (paclitaxel or docetaxel, carboplatin, trastuzumab)
- TCHP (paclitaxel or docetaxel, carboplatin, trastuzumab, pertuzumab)
- TH (paclitaxel, trastuzumab)
Hormonal therapy
Hormonal therapy types
- Gonadotropin or luteinizing releasing hormone (GnRH or LHRH) agonist medications are used to prevent the ovaries from producing estrogen, resulting in temporary menopause. These medications include goserelin (Zoladex) and leuprolide (Eligard, Lupron). Because they are ineffective on their own in treating breast cancer, they are usually used in conjunction with other hormonal therapies. They are administered by injection every four weeks and prevent the ovaries from producing estrogen. When GnRH medicines are withdrawn, the side effects fade.
- Ovarian ablation uses a surgical procedure that removes the ovaries in order to cease estrogen production. While this is a permanent solution, it can be a viable alternative for women who no longer wish to become pregnant, especially since the long-term costs are often lower.
- Begin hormone replacement therapy with an AI. When AI is the only hormone therapy used, it is administered for 5 to 10 years.
- Begin hormone therapy with tamoxifen and then transition to an AI after a few years. When taking an AI following tamoxifen, the medications are taken for a total of 5 to 10 years.
- Tamoxifen for a period of 5 to 10 years
- An AI for 5 to 10 years.
- Tamoxifen for 5 years, then an AI for up to 5 years. This would amount to ten years of hormonal therapy.
- Tamoxifen for 2 to 3 years, then an AI for 2 to 8 years for a total of 5 to 10 years of hormone therapy.
- If a woman has not reached menopause after the first five years of medication and is advised to continue treatment, she can take tamoxifen for another five years, for a total of ten years. Alternatively, a woman could begin ovarian suppression and then switch to an AI for the next 5 years.
- If a woman experiences menopause within the first five years of treatment and is advised to continue treatment, she can take tamoxifen for another five years or switch to an AI for another five years. This would amount to ten years of hormonal therapy. Only definitely postmenopausal women should consider taking an AI.
- For young ladies who have been diagnosed with breast cancer.
- For women who are at high risk of recurrence of cancer.
- Chemotherapy is also suggested for women with stage II or stage III cancer. However, data currently reveals that there are benefits that are not contingent on the use of chemotherapy.
- For women with stage I or stage II cancer who are at a higher risk of recurrence, chemotherapy may be considered.
- For women who are unable to take tamoxifen due to other health issues, such as a history of blood clots, an AI drug is available.
- For women who have cancer, it is unlikely to recur.
- When chemotherapy is not indicated for women with stage I cancer.
Targeted therapy
HER2-targeted therapy
Bone modifying medications
- Bisphosphonates: These inhibit the osteoclasts, or bone-destroying cells.
- Denosumab (Prolia, Xgeva: A RANK ligand inhibitor is an osteoclast-targeted treatment. The American Society of Clinical Oncology (ASCO) does not suggest using denosumab as an adjuvant treatment to prevent breast cancer recurrence.
Other types of targeted therapy for breast cancer
- Olaparib (Lynparza): Olaparib is a kind of antibiotic (Lynparza). This is a PARP inhibitor, which is a sort of oral medicine that eliminates cancer cells by stopping them from repairing damage to the cells. ASCO recommends olaparib for the treatment of early-stage, HER2-negative breast cancer in persons with a hereditary BRCA1 or BRCA2 gene mutation and a high risk of breast cancer recurrence. Adjuvant olaparib should be administered for a year following the completion of chemotherapy, surgery, and radiation therapy (if needed).
- Abemaciclib (Verzenio): This oral medicine, known as a CDK4/6 inhibitor, targets a protein called CDK4/6 in breast cancer cells, which may encourage cancer cell development. It is approved for use in conjunction with hormonal therapy (tamoxifen or an AI) to treat persons with hormone receptor-positive, HER2-negative early breast cancer that has progressed to the lymph nodes and is at high risk of recurrence. For patients who match these criteria, ASCO advises 2 years of abemaciclib medication paired with 5 years or more of hormonal therapy.
Neoadjuvant systemic therapy for non-metastatic breast cancer
Neoadjuvant systemic therapy options based on type of non-metastatic breast cancer
Immunotherapy
Concerns about systemic therapy for elderly individuals
Recurrent breast cancer
- In the same location as the original cancer. This is known as a local recurrence.
- The chest wall, as well as lymph nodes under the arm or in the chest on the same side as the original cancer. This is known as a localized recurrence.
- Another location, which includes distant organs such the bones, lungs, liver, and brain. This is referred as as a distant recurrence or metastatic recurrence.
- Previous treatment(s) for the cancer that was first discovered
- The amount of time since the initial diagnosis
- The occurrence’s location
- Tumor characteristics such as ER, PR, and HER2 status
Treatment options for a local or regional recurrence of breast cancer
- A mastectomy is frequently advised for women who have a local recurrence of breast cancer following initial treatment with a lumpectomy and adjuvant radiation therapy. With this treatment, the cancer is usually fully eradicated.
- The recommended treatment for women who have a local or regional recurrence in the chest wall after an initial mastectomy is surgical excision of the recurrence followed by radiation therapy to the chest wall and lymph nodes. However, if radiation therapy was already administered for the primary malignancy, this may not be an option. Radiation therapy cannot normally be administered to the same location at full dose more than once. Systemic therapy is sometimes used before surgery to shrink the malignancy and make it easier to remove.
- Radiation therapy, chemotherapy, hormone therapy, and targeted therapy are some of the various treatments utilized to lower the likelihood of a distant recurrence in the future. These are employed depending on the tumor and the type of previous treatment.