Stage 4 of breast cancer signifies that the breast cancer has metastasized to another part of the body; liver, brain, bones, and lungs are the most commonly invaded organs.
In stage 4 breast cancer, cancer cells escape from the primary tumor in the breast and reach other body parts through the blood circulation or the lymphatic system, an extensive network of vessels and nodes responsible for removing pathogens and cellular waste products.
Usually, breast cancer appears back in a different part of the body even after it goes into remission—approximately 30% of women with early-stage breast cancer develop metastatic breast cancer months or years after the initial diagnosis and treatment.
Some people already have metastatic disease at the first breast cancer diagnosis, known as de novo metastatic breast cancer (dnMBC). dnMBC means that cancer in the breast remained undetected before it spread to a distant body part.
A metastatic tumor that develops in a different body site is made up of breast cancer cells, not the cells of invaded tissue or organ. Therefore, if breast cancer spreads to the lungs, the lung's metastatic tumor is formed from breast cancer cells, not lung cells.
The symptoms of metastatic breast cancer often vary from those of early-stage breast cancer. It is also possible that the patient may not experience any symptoms at all.
Some of the common signs and symptoms of metastatic breast cancer include:
Pain in bones or bone fractures
Breathlessness or chest pain
Dizziness or headaches
Swollen stomach or jaundice
The breast cancer stage 4 symptoms may also differ depending on the area of body cancer has reached.
Although metastatic tumors can grow in any part of the body, breast cancer cells are more likely to travel to certain places, which include the lymph nodes, bones, lungs, liver, and brain.
The lymph nodes present near the collarbone, beneath the arms, and inside the breasts happen to be the first places cancer cells spread towards. The cancer is metastatic if it travels beyond these tiny glands and settles in distant body parts. The patient might not observe any indications until the breast cancer is confined to these nodes.
When breast cancer has metastasized to bones, the patient usually feels pain as the first symptom. Any bone may get affected, such as the arms, spine, and legs. Cancer can weaken the bones to the point of breaking, but this can be prevented by treatment. The cancerous invasion of the spine can result in urinary incontinence. The person may also feel numbness in one or more of their limbs.
Breast cancer stage 4 tumors can form on the lungs or the region between the chest wall and lung, causing fluid to build up around the affected area. Manifestations are shortness of breath, persistent cough, and chest pain.
If breast cancer reaches the liver, the person may feel persistent pain in the belly or bloating and fullness, leading to loss of appetite and weight. The person may notice their eyes and skin turning yellow because of jaundice. All these symptoms occur due to improper functioning of the liver.
Nearly 10-15% of stage IV breast cancer female patients develop brain metastases. If breast cancer spreads to the brain, it causes headaches, memory problems, mood swings or personality changes, seizures, slurred speech, balance problems, blurred vision, and dizziness. The affected person may experience numbness or weakness in one or more body parts.
Breast cancer has several types, and all of these types can metastasize. In the majority of cases, breast cancers originate in the ducts (ductal carcinomas) or lobules (lobular carcinomas):
Ductal carcinoma: These cancers begin in the cells that line the milk ducts and are the most common breast cancers.
Lobular carcinoma: This cancer occurs in the milk-producing structures or glands (lobules).
The other types of breast cancer involve:
Inflammatory breast cancer (making up for almost 2% to 4% of all breast cancer cases in the US and is one of the faster-growing types of cancer)
Paget's disease (a type of breast cancer that occurs in the nipple's ducts)
Both women and men can develop breast cancer. However, it is rare in men (accounting for less than 1% of all cases reported yearly).
Breast cancer has four main molecular subtypes, primarily defined by hormone receptors (HR) and the involvement of different proteins in each tumorous growth in breasts.
Luminal A tumors are the most common and tend to have slower growth than other subtypes. These cancers are referred to as HR-positive because experts characterize them by their hormone receptors, particularly as estrogen receptor (ER)-positive progesterone receptor (PR)-positive, or both. ER-positive cancer grows from the hormone estrogen, and PR-positive cancer's growth depends on progesterone. Medications that decrease the levels of these hormones prove helpful in treating this category of breast cancer.
Luminal A breast tumors are also classified as HER2-negative. HER2 (human epidermal growth factor receptor-2) is a protein that performs a vital function in developing and repairing healthy breast cells from a gene-centered viewpoint. A breast cancer patient has HER2-negative cancer if no significant variation in HER2 serum levels is observed compared to healthy individuals.
Luminal B cancer cells proliferate quicker than luminal A cancer cells and have a more aggressive nature. They are both HR-positive and HER2-positive (a higher-than-average number of HER2 genes are present in the individual).
Around 15% to 20% of breast cancers are "HER2-positive", which means these cancers have more than normal levels of the HER2 protein or numerous copies of the HER2 gene. HER2 proteins, also called "receptors," are essential for the development and growth of these tumors. In contrast to other types, HER2-positive breast cancers grow and spread quickly.
If a patient's tumor does not express any of all three receptors, PR, ER, or HER2, the cancer is termed as "triple-negative." Triple-negative breast cancers account for almost 10-15% of invasive breast cancers. This breast cancer type appears to be more prevalent in younger females, especially young Black women. TNBC exhibits rapid progression and metastasis. It is the most common breast cancer type among women with a BRCA1 gene mutation.
According to the American Cancer Society, from 2019 to 2020, about 73% of all breast cancer cases reported in the United States are luminal A, 11% are luminal B, 12% are triple-negative, and 4% are HER2-enriched.
In American women, breast cancer is the commonest cancer (except skin cancer) and the second most prevailing cause of mortality from cancer. Almost 6% of women already have metastatic disease when they are diagnosed. Further research is required to determine the percentage of non-metastatic breast cancer survivors predisposed to develop metastatic breast cancer later.
According to the American Society of Clinical Oncology (ASCO) and other reliable sources, in 2021, 284,200 people (2,650 men and 281,550 women) are expected to be diagnosed with metastatic breast cancer in the United States.
It is estimated that breast cancer will cause the death of 44,130 people (530 men and 43,600 women) this year, with metastatic breast cancer resulting in the majority of these deaths.
According to the SEER database, approximately 27% of people in the United States live at least five years following a stage 4 breast cancer diagnosis.
Various factors influence the expectancy and quality of a patient's life. Each subtype of breast cancer behaves uniquely. Some are more challenging to treat, and some have far more sporadic treatment options, and this way, the person's subtype may affect their chances of recovery.
The lesser the extent of metastasis, the higher the rate of survival will be. The affected person may have a better long-term outlook if their cancer has only spread to bones or lungs, rather than bones and lungs both.
Seeking treatment immediately and making good lifestyle choices would also increase the chances of survival.
Patients with stage IV breast cancer often receive systemic (drug) therapies as the primary treatments. These may include:
Some combination of these
Apart from medicinal treatment, surgical removal of tumors and radiation therapy can help in some conditions.
Treatment usually decreases the size of tumors or retard their growth, eases symptoms, and increases life expectancy. Although the proper treatment improves the person's condition, stage 4 breast cancer is considered incurable.
It is now possible to measure the number of cancer tumor cells circulating in the patient's blood at Silver Cancer Institute and Center for Chronic Disease. The analysis of liquid biopsies helps Dr. Dean R. Silver predict the extent of cancer spread and conclude whether the disease will reoccur after treatment. SCI offers personalized treatments for all the patients based on the evaluation of the genetic mutations of each case of cancer.
Low-dose Chemotherapy and Natural Substances - Metronomic chemotherapy is administered to the patient depending on the low testing dose. The use of low-dose chemotherapy does not result in chemoresistance, and adverse effects on the patient's immune system are less likely to occur. The toxic effects of the chemotherapeutic drugs are avoided by supplementing the patient's body with natural substances. These natural substances are synergistic with other treatments and kill the cancer cells directly. As confirmed by modern research, decreasing chemotherapy resistance will enhance the patient's immune status and improve prognosis.
Immunotherapy with Checkpoint Inhibitors - Utilizing checkpoint inhibitors in combination with chemo and radiation therapy is gaining popularity as the standard of care. All targeted therapies help block the biomarkers, which are the driving factors for cancer's growth.
Autologous whole cancer vaccine, Dendritic cell vaccine, and Supportive Oligonucleotides (SOT) - Personalized vaccines for stage IV breast cancer are currently being created in the Silver Cancer Institute's laboratory using the cancer cells obtained from the patient's blood. Patients are given these vaccines several times a year to attack cancer and prevent recurrences.
All of these different modalities are combined in a synergistic additive manner to make the treatment plan successful.