Types of Treatment for Breast Cancer in Men

Executive Summary

The different types of standard treatments for breast cancer in men is explained in detail. Standard treatments are used along with the integration of effective treatment planning. Clinical trials are used as an innovative treatment approach that combines different therapies and drugs for treating breast cancer in men. In the case of DCIS and early-stage invasive breast cancer, the doctors recommend surgery to remove the tumor as the first treatment. Systemic treatment is suggested with chemotherapy or hormonal therapy before surgery (neoadjuvant or preoperative) for rapidly growing larger or smaller cancers. Other treatment approaches involve surgery (lumpectomy and mastectomy), lymph node removal and analysis (sentinel lymph node biopsy and axillary lymph node dissection), radiation therapy, chemotherapy, hormonal therapy, targeted therapy, HER2-targeted therapy, bone modifying drugs, and immunotherapy. Palliative care is provided to the patients to cope with mental, physical or financial issues while involving medication, nutritional changes, emotional and spiritual support and other relaxation therapies.

Treatments of Breast Cancer in Men

“Standard to care” refers to the best-known treatment. In cancer care, different doctors work together to bring out an overall treatment plan for the patient. This is called a multidisciplinary team. 

Treatments recommendations depend on many factors:

• The size, grade and type of tumour
• The tumour’s subtype, including hormone receptor status (ER, PR) and HER2 status 
• The patient’s age, general health, and preferences
• Genomic markers, like Oncotype DX™ or Mammaprint™ 
• Known mutations in inherited breast cancer genes, like BRCA1 or BRCA2

Although the breast cancer care team will tailor the treatment for the patient and the breast cancer, some generalized steps for treating breast cancer.

For DCIS and early-stage invasive breast cancer, doctors usually suggest surgery to remove the tumour as the first treatment. The surgeon will remove a small area of normal healthy tissue around the tumour to ensure that the entire tumour is removed. Although surgery aims to remove all visible cancer, microscopic cells can remain in the breast or elsewhere after surgery. In a few situations, this means that another surgery may be needed to remove the remaining cancer cells.

For larger or smaller cancers growing more quickly, doctors may suggest systemic treatment with chemotherapy or hormonal therapy before surgery, known as neoadjuvant or preoperative therapy. There can be several benefits to having other treatments before surgery-

• Surgery may be easier to perform afterwards.
• The doctor may find out if specific treatments work well for cancer.
• You may try a new treatment in a clinical trial.

Surgery

Surgery is used to evaluate the nearby underarm or axillary lymph nodes ^​1​. 

• A lumpectomy removal of the tumour and a small, cancer-free margin of healthy tissue around the tumour. If there is no large breast tissue, a lumpectomy may not be an alternative.
• A mastectomy is the surgical removal of the complete breast. This is the commonly performed procedure in men.

If surgery for the cancer is not possible, it is called inoperable or unresectable. The doctor will then suggest treating cancer in other ways. Chemotherapy, radiation therapy, targeted therapy, or hormonal therapy may shrink cancer.

Lymph node removal and analysis

Cancer cells can be seen in the axillary lymph nodes in some cancers. It is essential to find out whether any lymph nodes near the breast contain cancer. This information is used to find treatment and prognosis. Most invasive cancer patients will have either an axillary lymph node dissection or a sentinel lymph node biopsy.

• Sentinel lymph node biopsy – In a sentinel lymph node biopsy (also called SNB), the surgeon finds and removes one to three or more lymph nodes from under the arm that receives lymph drainage from the breast. This procedure helps avoid removing many lymph nodes with an axillary lymph node dissection for patients whose sentinel lymph nodes are mostly cancer-free. The smaller lymph node procedure helps decrease the risk of several possible side effects, including numbness, swelling of the arm (lymphedema), arm movement and range of motion problems. Importantly, the chances of lymphedema increase with the number of lymph nodes and lymph vessels removed or damaged during treatment. This means that men with a sentinel lymph node biopsy tend to be less likely to develop lymphedema than those with an axillary lymph node dissection.
• In a sentinel lymph node biopsy, the surgeon searches and removes a small number of sentinel lymph nodes underarm that receives lymph drainage from the breast. To find the sentinel lymph node, the surgeon injects a dye or a radioactive tracer into the area of cancer or around the nipple.
• If the sentinel lymph node is cancer-free, research shows that it is likely that the remaining lymph nodes will also be cancer-free. This means that no more lymph nodes are required to be removed. Suppose only one or two sentinel lymph nodes have cancer, and you plan to have radiation therapy and a lumpectomy to the entire breast. In that case, an axillary lymph node dissection may not be needed. In general, sentinel lymph node biopsy is the standard of care for most men with early-stage breast cancer that can be removed with surgery and whose underarm lymph nodes are not enlarged. However, it may be appropriate not to undergo axillary surgery in certain situations. 
• A sentinel lymph node biopsy alone may not be performed if there is obvious evidence of cancer in the lymph nodes before surgery. In this situation, a complete axillary lymph node dissection is preferred.
• Axillary lymph node dissection – The surgeon removes many lymph nodes under the arm in an axillary lymph node dissection. These are then examined for cancer cells. The actual amount of lymph nodes removed varies in each person. An axillary lymph node dissection may not be required for all men with early-stage breast cancer with tiny amounts of cancer in the sentinel lymph nodes. Men with a lumpectomy and radiation therapy with a smaller tumour (less than 5 cm) and no more than two sentinel lymph nodes with cancer may avoid a complete axillary lymph node dissection. This helps lower the risk of side effects and doesn’t decrease survival if cancer is found in the sentinel lymph node, whether additional surgery is required to remove more lymph nodes.

Most invasive breast cancer patients will have an axillary lymph node dissection or a sentinel lymph node biopsy. However, these procedures can be optional for some patients older than 65. This depends on how significant the lymph nodes are, the tumour’s stage, and the person’s overall health.

Summary of surgical options

Surgical treatment options include the following –

• Lymph node evaluation through a sentinel lymph node biopsy or axillary lymph node dissection
• Removal of cancer in the breast through either mastectomy or lumpectomy

Before surgery, talk to the health care team about the possible side effects of the specific surgery.

Radiation therapy

Radiation therapy uses high-energy X-rays to kill cancer cells. A radiation therapy schedule consists typically of a specific number of treatments offered over a set period.

The most common radiation treatment type is external-beam radiation therapy, given from a machine outside the body. When radiation treatment is provided with a probe in the operating room, intra-operative radiation therapy is performed. If radiation therapy is given by placing radioactive sources into the tumour, it is known as brachytherapy. Even though the research results are encouraging, intra-operative radiation therapy and brachytherapy are not used widely for breast cancer. These radiation therapies are typically only used for small cancer that has not spread to the lymph nodes. 

Adjuvant radiation therapy is suggested for some men depending on the type of surgery, the size of their tumor, the number of cancerous lymph nodes under the arm, and the width of the tissue margin around the tumor removed by the surgeon ^​2​.

Radiation therapy can cause side effects, including swelling of the breast, fatigue, pain or burning in the skin where the radiation was directed, redness or skin discolouration or hyperpigmentation, and sometimes with peeling or blistering. Very rarely, a small part of the lung can be affected by the radiation, leading to pneumonitis, a radiation-related swelling of the lung tissue. This risk depends on the area that received radiation therapy, and it tends to heal with time. In older times, with old equipment and radiation therapy techniques, people who received treatment on the left side of the body slightly increased the long-term risk of heart disease. Modern techniques, like respiratory gating, which uses technology to guide the delivery of radiation while a patient breathes, can spare the vast majority of the heart from the effects of radiation therapy.

Chemotherapy

Chemotherapy uses medicine to kill or stop the growth of cancerous cells. Depending upon the stage, different chemotherapy is given. The point that makes a difference is how the chemotherapy enters the body and which cells it affects.

Some patients may receive chemotherapy post-surgery from killing left out cancerous cells, called adjuvant chemotherapy, while some may receive chemotherapy first called neoadjuvant therapy.

Chemotherapy is given to lower the chances of recurrence of breast cancer. It is also used to shrink a large tumor and make surgery easier when given before surgery. 

A chemotherapy schedule usually consists of a certain number of cycles over a fixed period. A patient can be given one drug at a time or a combination of different drugs given simultaneously. Chemotherapy may be provided on different schedules depending on what worked best in the clinical trials for that particular type of regimen. It can be given once a week, once every two weeks, once every three weeks, or even once every four weeks. Common types of chemotherapy used to treat locally advanced, early-stage, or metastatic breast cancer include ^​3​ –

• Cyclophosphamide (available as a generic drug)
• Capecitabine (Xeloda, available as a generic drug)
• Carboplatin (available as a generic drug)
• Cisplatin (available as a generic drug)
• Doxorubicin (available as a generic drug)
• Docetaxel (Taxotere, available as a generic drug)
• Eribulin (Halaven)
• Epirubicin (Ellence, available as a generic drug)
• Fluorouracil (5-FU, available as a generic drug)
• Ixabepilone (Ixempra)
• Gemcitabine (Gemzar)
• Methotrexate (Trexal, Rheumatrex, available as a generic drug)
• Pegylated liposomal doxorubicin (Doxil, available as a generic drug)
• Protein-bound paclitaxel (Abraxane)
• Paclitaxel (Taxol, available as a generic drug)
• Vinorelbine (Navelbine, available as a generic drug)

Research has shown that combinations of specific drugs are sometimes more effective than single drugs for adjuvant treatment. The following combinations of drugs can be used as adjuvant therapy to treat breast cancer –

• AC or EC (epirubicin and cyclophosphamide or doxorubicin and cyclophosphamide) followed by T (paclitaxel or docetaxel)
• AC (doxorubicin and cyclophosphamide)
• CEF (cyclophosphamide, epirubicin, and 5-FU)
• CAF (cyclophosphamide, doxorubicin, and 5-FU)
• CMF (cyclophosphamide, methotrexate, and 5-FU)
• EC (epirubicin and cyclophosphamide)
• TC (docetaxel and cyclophosphamide)
• TAC (docetaxel, doxorubicin, and cyclophosphamide)

Therapies that target the HER2 receptor can be given with chemotherapy for HER2-positive breast cancer.

The chemotherapy side effects depend on the patient, the drug used, and the schedule and dose. These side effects can include the risk of infection, fatigue, nausea and vomiting, hair loss, loss of appetite, numbness and tingling, and diarrhoea or constipation. These side effects can usually be prevented or managed during treatment with supportive medications, including boosting the immune system. Most side effects usually go after treatment is completed. Some side effects, like tingling and numbness of the fingers and toes and loss of fertility, can continue after treatment. Rarely, long-term side effects may occur, like secondary cancers or heart damage. Many patients feel well during chemotherapy and actively take care of their families work and exercise during treatment. But each person’s experience is different. Talk to the health care team about the possible side effects of your chemotherapy plan.

Hormonal therapy

Hormonal therapy, known as endocrine therapy, is an essential treatment for tumours that test positive for estrogen or progesterone receptors (ER-positive or PR positive). Hormone receptor-positive tumours use hormones to fuel their growth. Blocking the body’s hormones can then slow the growth of the tumour and kill the cancer cells. Since most men with breast cancer have ER-positive disease, hormonal therapy is mostly part of the treatment plan.

ASCO suggests that men who have had surgery to remove a hormone receptor-positive breast cancer receive hormonal therapy for at least five years. It may be taken for up to ten years, especially if cancer has a higher chance of returning. How long should hormonal therapy be continued depends on the cancer stage, the risk of it returning, and any side effects you are experiencing.

Hormonal therapy post-surgery can be used by itself or after chemotherapy ^​4​. Hormonal therapy options for men include –

• Tamoxifen (available as a generic drug) –  For men with all stages of hormone receptor-positive breast cancer, ASCO suggests tamoxifen as the primary hormonal therapy. Tamoxifen blocks estrogen from binding to breast cancer cells. If a man having breast cancer has taken tamoxifen for five years without serious side effects and still has a high risk of cancer coming back, five more years of tamoxifen therapy can be offered.

• Aromatase inhibitors (AIs, all available as generic drugs) include exemestane (Aromasin), anastrozole (Arimidex), and letrozole (Femara). AIs decrease the amount of estrogen formed by the body. This type of treatment effectively treats all stages of breast cancer in postmenopausal women, but there is not much information on AI use for men with breast cancer. Caution is urged in using AIs in men who still have their testicles, as these treatments could cause an increase in androgen levels. An additional medication to decrease androgen production may also be offered if an AI is used.
• Fulvestrant (Faslodex) is a drug given by injection once a month. It is used for the treatment of metastatic breast cancer. It stops estrogen from helping cancer grow differently from tamoxifen. Like AIs, there is not much information on their use for men, but research has shown that it may be effective.

Side effects of hormonal therapy can include decreased sexual desire or ability, hot flashes, mood swings, leg cramps, bone loss, and blood clots.

Men with breast cancer should not receive androgen or testosterone supplementation.

Targeted therapy

Targeted therapy aims at any factor contributing to the growth and development of cancer cells. It can be a specific protein, gene or tissue environment. These treatments are typical and do not harm surrounding cells like those in chemotherapy or Radiotherapy.

Not all tumours have the same cellular traits, so doctors may recommend testing to understand better changes in the individual tumour’s genes and proteins.

In addition, research studies continue to search more about specific molecular targets and new treatments directed at them. 

Hormonal therapies were the first approved targeted therapies for breast cancer. Then, HER2-targeted therapies were approved to treat HER2-positive breast cancer. Targeted therapies are used to treat metastatic breast cancer.

HER2-targeted therapy

• Trastuzumab (Herzuma, Herceptin, Ogivri, Ontruzant, Hylecta) – This drug is approved as adjuvant therapy for non-metastatic HER2-positive breast cancer and the treatment of metastatic HER2-positive breast cancer. Currently, most patients with stage I – stage III breast cancer should receive a trastuzumab-based regimen, mostly including a combination of trastuzumab with chemotherapy, followed by one year of adjuvant trastuzumab. Trastuzumab is often combined with chemotherapy or other targeted drugs for patients with metastatic breast cancer. Patients receiving trastuzumab have a slight (2% to 5%) risk of heart problems. This risk is increased if a patient has other risk factors for heart disease or receives chemotherapy that also increases the risk of heart problems simultaneously. These heart problems may go and can be treatable with medication. This drug is given by injection (Hylecta) every three weeks or by vein every 1 to 3 weeks.
• Pertuzumab (Perjeta) – This drug is approved for stage II and stage III breast cancer and metastatic breast cancer combined with trastuzumab and chemotherapy. This drug can cause diarrhoea and skin rash. This drug is given by vein every three weeks.
• Pertuzumab, trastuzumab, and hyaluronidase–zzxf (Phesgo) – This combination drug contains pertuzumab, trastuzumab, and hyaluronidase-zzxf in a single dose, is approved for people with early-stage HER2-positive breast cancer. It can be given in combination with chemotherapy. It is provided by injection under the skin and can be administered either at a treatment centre or at home by a healthcare professional.
• Ado-trastuzumab emtansine or T-DM1 (Kadcyla) is approved to treat patients with early-stage breast cancer who have had treatment with trastuzumab and chemotherapy with either docetaxel or paclitaxel followed by surgery and who had cancer remaining (or present) at the time of surgery. It is also approved for the treatment of metastatic HER2 positive breast cancer. T-DM1 is a combination of trastuzumab linked to a very small quantity of strong chemotherapy—this helps to deliver chemotherapy into the cancer cell while lessening the chemotherapy received by healthy cells. T-DM1 is given by vein every three weeks.
• Trastuzumab deruxtecan (Enhertu) – Trastuzumab deruxtecan is approved to treat patients with metastatic HER2-positive breast cancer who have already received two or more HER2-targeted therapies. This HER2-targeted treatment is a combination of a drug similar to trastuzumab, known as a biosimilar, linked to a small amount of strong chemotherapy. The trastuzumab biosimilar carries the chemotherapy to the HER2-positive cancer cells, killing the cancer cells and limiting damage to healthy cells. It is given by vein every three weeks. The treatment has a low risk of interstitial lung disease (ILD), which causes scarring of the lungs and can make breathing difficult or cause coughing.
• Tucatinib (Tukysa) – Tucatinib, added to capecitabine chemotherapy and trastuzumab, is approved to treat advanced unresectable or metastatic HER2-positive breast cancer, including cancer that has reached the brain, in those who have already received one or more HER2-targeted therapy. Tucatinib is a tyrosine kinase inhibitor designed to turn off HER2. It is an oral drug that is given twice daily. This drug can cause diarrhoea and affect the liver.
• Neratinib (Nerlynx) – In combination with capecitabine chemotherapy, Neratinib is approved to treat higher-risk HER2-positive, early-stage breast cancer. It is taken for a year, starting after patients have finished one year of trastuzumab. It is also approved to treat advanced or metastatic HER2-positive breast cancer in patients who have already received two or more HER2-targeted therapies. Neratinib is a tyrosine kinase inhibitor. It is an oral drug that is given every day for three weeks. This drug can cause diarrhoea and can also affect the liver.
• Lapatinib (Tykerb) – Men with HER2-positive metastatic breast cancer may benefit from lapatinib when other medications are no longer effective at controlling cancer’s growth. The combination of lapatinib and the chemotherapy capecitabine has been approved to treat metastatic HER2-positive breast cancer when a patient has received chemotherapy and trastuzumab already. The combination of lapatinib and letrozole is also approved for ER-positive cancer and metastatic HER2-positive. Lapatinib is also used with trastuzumab for patients whose cancer is growing while receiving trastuzumab. Lapatinib may enter the brain and could be an option for HER2-positive breast cancer that has reached the brain. This drug can affect the liver and can cause diarrhoea.

Combination regimens for stages I to III, HER2-positive breast cancer include – 

• AC-TH (cyclophosphamide, doxorubicin, paclitaxel, trastuzumab)
• TCH (docetaxel or paclitaxel, carboplatin, trastuzumab)
• AC-THP (doxorubicin, cyclophosphamide, paclitaxel, trastuzumab, pertuzumab)
• TH (paclitaxel, trastuzumab)
• TCHP (carboplatin, docetaxel or paclitaxel, trastuzumab, pertuzumab)

Bone modifying drugs

Bone modifying drugs help strengthen the bone and block bone destruction. They are mainly used to treat cancer that has spread to the bone. For people whose cancer has not spread, bone modifying drugs may be used to help keep cancer from recurring. Certain types are used in low doses to prevent and treat osteoporosis. Osteoporosis is the thinning of the bones. ASCO suggests that men with early-stage breast cancer that has not proliferated to the bone shouldn’t be treated with bone modifying drugs to prevent a recurrence. Still, they could receive these drugs to prevent or treat osteoporosis.

There are two types of drugs that block bone destruction:

• Bisphosphonates- These block the cells that destroy bone, called osteoclasts. Bisphosphonates include the medicines zoledronic acid (Reclast), Fosamax), alendronate (Binosto), and ibandronate (Boniva).
• Denosumab (Prolia)- An osteoclast-targeted therapy known as RANK ligand inhibitor.

Other targeted therapy for breast cancer

You may have other targeted options for breast cancer in men treatment, depending on several factors. Many of the below-mentioned drugs are used for metastatic or advanced metastatic breast cancer.

• Alpelisib (Piqray) – Alpelisib is an option along with the hormonal therapy fulvestrant for women and men with hormone receptor-positive, HER2-negative metastatic breast cancer with a PIK3CA gene mutation and has worsened during or post-hormonal therapy.
• Drugs that target the CDK4/6 protein in breast cancer cells can stimulate cancer cell growth. These drugs include palbociclib (Ibrance), abemaciclib (Verzenio), and ribociclib (Kisqali). They are approved for HER2-negative advanced or metastatic breast cancer, and ER-positive can be combined with other types of hormonal therapy.
• Larotrectinib (Vitrakvi) – Larotrectinib is for breast cancer with an NTRK fusion that is metastatic or cannot be removed using surgery and has worsened with other treatments.
• Olaparib (Lynparza) – This oral drug can be used for patients with metastatic HER2-negative breast cancer and a gene mutation of BRCA1 or BRCA2 who have previously received chemotherapy. A type of drug called a PARP inhibitor destroys cancer cells by preventing them from fixing the damage.
• Talazoparib (Talzenna) – Talazoparib is an oral drug that can treat patients with metastatic or locally advanced HER2-negative breast cancer having a BRCA1 or BRCA2 gene mutation.
• Sacituzumab govitecan-hziy (Trodelvy) – In 2020, the U.S. Food and Drug Administration (FDA) approved using sacituzumab govitecan-hziy for the treatment of people having metastatic triple-negative breast cancer who have already received at least two treatments. Sacituzumab govitecan-hziy is an antibody-drug conjugate. The antibody gets attached to the cancer cell and then delivers the anticancer drug it carries to start killing the cancer cell.

Immunotherapy 

Immunotherapy, a type of biological therapy, uses artificial or natural substances to harness our immune system to fight. It uses substances formed by the body or laboratory to improve, target, or restore immune system function. The following drugs, a type of immunotherapy known as immune checkpoint inhibitors, are used for advanced and recurrent or metastatic breast cancer. Pembrolizumab is used for high-risk, early-stage diseases.

• Pembrolizumab (Keytruda) is a type of immunotherapy that the FDA approves to treat both early-stage, high-risk triple-negative breast cancer and metastatic cancer or cancer that can’t be treated with surgery. Pembrolizumab is approved to treat people with early-stage, high-risk, triple-negative breast cancer combined with chemotherapy before the surgery. It can then continue to be given alone following surgery. For people having metastatic breast cancer, pembrolizumab is approved in combination with some different chemotherapy drugs to treat locally recurrent or metastatic triple-negative breast cancer that can’t be treated with surgery and that tests positive for PD-L1. Additionally, pembrolizumab can be used to treat people with metastatic breast cancer whose tumours have a molecular alteration called DNA mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H).
• Dostarlimab (Jemperli) – The FDA approves this type of immunotherapy to treat metastatic or recurrent breast cancers with dMMR and have progressed during or after the last treatment.

Different types of immunotherapy can lead to various side effects. Common side effects include flu-like symptoms, skin reactions, diarrhoea, and weight changes. Talk to the doctor about the possible side effects of the immunotherapy recommended for you. 

Palliative Care 

Cancer and its treatment have side effects that can be mental, physical or financial and managing the effects are palliative or supportive care.

Palliative care includes medication, nutritional changes, emotional and spiritual support and other relaxation therapies. 

Palliative care focuses on alleviating how you feel during treatment by managing symptoms and supporting patients and their families with other non-medical needs. Regardless of type and stage of Cancer age, any person may receive this type of care.

Recurrent Breast Cancer

If cancer returns post-treatment for early-stage disease, it is known as recurrent cancer. When breast cancer recurs, it may return in the following parts of the body –

• The same place as original cancer- a local recurrence.
• The lymph nodes under the arm, chest, or chest wall – locoregional recurrence.
• A location distant from the breast, including bones, liver, lungs, and brain – distant or a metastatic recurrence.

When breast cancer recurs, a new testing cycle will start again to learn about the recurrence. Testing may include imaging tests, like those discussed in the Diagnosis section. Additionally, a biopsy may be needed to confirm the breast cancer recurrence and learn about the features of cancer.

After this testing ends, you and your doctor will talk about the options available for treatment. The treatment plan can include some of the treatments described above, like surgery, chemotherapy, radiation therapy, targeted therapy, and hormonal therapy. The treatment options depend on the mentioned factors-

• Previous treatment for the original cancer
• Time since the initial diagnosis
• Characteristics of the tumor, like ER, PR, and HER2 status
• Location of the recurrence

If treatment doesn’t work

If cancer can’t be treated or controlled, it leads to advanced or terminal cancer. It is vital to have straightforward conversations with your health care team to express your feelings, preferences, and concerns. The health care team has unique skills, knowledge, and experience to assist patients and their families. Ensuring that a person is physically comfortable, free from pain, and emotionally supported is extremely important.

References