The Extrinsic Effect Of Targeted Therapy
Fig. 4: The effects of cell-extrinsic and cell-intrinsic determinants in dictating breast cancer outcomes.
Part I The journey of a breast cancer patient from the development of undetectable disease and its clinical discovery , through its surgical removal and adjuvant ET , to metastatic relapse and death . The presence of tumour lesions across the body is indicated by starsthe smaller referring to the clinically undetectable ones , the bigger ones to the clinically detectable ones . Part II The development of an HR+ breast tumour lesion in the breast , comprising a mixture of ER+/PR+ and ER/PR cells . DTC escape from the primary site can occur early and/or late during tumorigenesis , although the HR phenotype of DTCs at these stages is often unclear. Bones, lungs and liver are represented as common secondary sites for breast cancer metastases, albeit the sequential patterns of DTC spread among these organs are still elusive . Targeted treatment for HR+ breast cancer patients relies on adjuvant ET. Several mechanisms of ET resistance cytostasis, ESR1 mutations and HR function regulationcontribute to DTC outgrowth. DTC disseminated tumour cell, ER oestrogen receptor, ET endocrine therapy, HR hormone receptor, PR progesterone receptor. Figure created with BioRender.com.
Benefits Of Primary Tumor Surgery In Patients Subdivided By Molecular Subtypes And Metastatic Sites
In the whole cohort, primary tumor surgery could prolong OS . In terms of molecular subtypes, surgery provided extra survival benefit in all subtypes . In terms of metastatic burden, BOM, bone and liver metastasis as well as bone and lung metastasis patients could benefit from surgery . However, surgery did not significantly benefit patients with bone and brain metastasis . Similarly, the analysis of BCSS showed consistent results.
Figure 4 Survival of de novo bone metastatic patients in different subtypes according to primary surgery. OS and BCSS in patients with HR+/HER2 tumors OS and BCSS in patients with HR+/HER2+ tumors OS and BCSS in patients with HR/HER2+ tumors OS and BCSS in patients with HR/HER2 tumors.
Figure 5 Survival of de novo bone metastatic patients in different metastatic burdens according to primary surgery. OS and BCSS in patients with bone-only metastasis OS and BCSS in patients with bone and brain metastasis OS and BCSS in patients with bone and liver metastasis OS and BCSS in patients with bone and lung metastasis.
High Blood Calcium Levels
When cancer spreads to the bones, too much calcium from the bones can be released into the bloodstream. This is called hypercalcemia.
High blood calcium levels can cause problems such as
- Feeling thirsty all the time and drinking lots of liquids
- Muscle weakness
- Kidney failure.
Treatment includes giving large amounts of intravenous fluids to protect the affected kidneys and medicines such as bisphosphonate drugs to bring blood calcium levels down quickly. Once the calcium level is back to normal, treating the cancer can help keep the calcium level from getting too high again.
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Metastatic Breast Cancer Treatment And Planning
After a diagnosis of metastatic breast cancer, its helpful to take all the time you need to gather information and make decisions about your treatment. Learn about the medical specialists that may be involved in your care, treatment options, genetic testing, taking a break from treatment, and more.
SurgeryDoctors sometimes recommend surgery for metastatic breast cancer in order, for example, to prevent broken bones or cancer cell blockages in the liver. Learn more.
ChemotherapyChemotherapy is used in the treatment of metastatic breast cancer to damage or destroy the cancer cells as much as possible. Learn more.
Radiation TherapyYour doctor may suggest radiation therapy if youre having symptoms for reasons such as easing pain and controlling the cancer in a specific area. Learn more.
Hormonal TherapyHormonal therapy medicines are used to help shrink or slow the growth of hormone-receptor-positive metastatic breast cancer. Learn more.
Targeted TherapyTargeted therapies target specific characteristics of cancer cells, such as a protein that allows the cancer cells to grow in a rapid or abnormal way. Learn more.
Local Treatments for Distant Areas of MetastasisLocal treatments are directed specifically to the new locations of the breast cancer such as the bones or liver. These treatments may be recommended if, for example, the metastatic breast cancer is causing pain. Learn more.
Metastasis Is A Highly Inefficient Yet Lethal Process
In the next few sections, we introduce the concept of tumour dormancy and discuss its ties with DTC dissemination in order to highlight how its reversible nature might alter the equilibrium between unsuccessful and successful metastases, thus possibly dictating the timing of metastatic relapse, or whether relapse occurs at all. We then focus on two key determinants of relapse in HR+ breast cancer: the extrinsic effect of targeted therapy, and the consequences of intrinsic HR function modulation.
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Symptoms If Cancer Has Spread To The Lymph Nodes
Lymph nodes are part of a system of tubes and glands in the body that filters body fluids and fights infection.
The most common symptom if cancer has spread to the lymph nodes is that they feel hard or swollen. You might have any of the following symptoms if your cancer has spread to the lymph nodes:
- a lump or swelling under your armpit
- swelling in your arm or hand
- a lump or swelling in your breast bone or collar bone area
One of the first places breast cancer can spread to is the lymph nodes under the arm on the same side as the breast cancer. This is not a secondary cancer.
Drugs To Treat Bone Metastases
The drugs used most often for treating bone problems in people with bone metastases are the bisphosphonate drugs pamidronate and zoledronic acid and the drug denosumab . These drugs are given intravenously or subcutaneously . Most patients are treated once a month at first, but may be able to be treated less often later on if they are doing well. Treatment with one of these drugs can help prevent further bone damage and events related to weakened bones such as fractures, hypercalcemia, and spinal cord compression.
These treatments can have a rare but serious side effect called osteonecrosis of the jaw . Patients complain of pain and doctors find that part of the jawbone has died. This can lead to an open sore that doesnt heal or tooth loss in that area. The jawbone can also become infected. Having jaw surgery or having a tooth removed can trigger this problem. It is best to avoid these procedures while you are taking one of these medicines. One way to avoid these dental procedures is to maintain good oral hygiene by flossing, brushing, making sure that dentures fit properly, and having regular dental checkups. Any tooth or gum infections should be treated right away. If ONJ does occur, the doctor will stop the bone medicine.
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What To Know About Breast Cancer Growth
Breast cancer occurs when normal cells mutate and multiply faster than usual. One cell divides to become two cells, then each of those cells divides to become four cells, and so on. The uncontrolled multiplication of cancer cells creates tumors within the breast tissue.
The speed at which a cancer progresses depends on the growth rate of the cancer cells. It is hard to estimate cancer growth because not all cancer cells multiply and divide at the same speed.
In most cases, breast cancer initially develops in either the milk ducts or the lobules, which are the glands that produce milk, before expanding into the breast tissue.
Breast cancer that develops in ducts or lobules can spread to the connective tissue. From there, it can spread to the surrounding lymph nodes.
Once in the lymph nodes, the cancer cells can enter the lymphatic system or the bloodstream, where they can move to other areas of the body.
Types Of Recurrent Cancer
There are three types of recurrent breast cancer:
Local recurrence: When cancer returns to the same part of the breast as the initial diagnosis, the disease is classified as a local recurrence.
Regional recurrence: This type is diagnosed when the breast cancer is found in nearby lymph nodes and/or the chest wall.
Distant recurrence: Also called metastatic breast cancer, this occurs when cancer cells travel away from the original tumor in the breast to other parts of the body through the lymphatic system or bloodstream. Common metastatic areas include the bones, liver and lungs. Even when a metastatic breast tumor spreads to a different part of the body, it contains the same cancerous cells that developed in the breast.
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Progression While Being Treated With Hormone Therapy
For hormone receptor-positive cancers that were being treated with hormone therapy, switching to another type of hormone therapy sometimes helps. For example, if either letrozole or anastrozole were given, using exemestane, possibly with everolimus , may be an option. Another option might be using fulvestrant or an aromatase inhibitor , along with a CDK inhibitor. If the cancer has a PIK3CA mutation and has grown while on an aromatase inhibitor, fulvestrant with alpelisib might be considered. If the cancer is no longer responding to any hormone drugs, chemotherapy is usually the next step.
Local Or Regional Treatments For Stage Iv Breast Cancer
Although systemic drugs are the main treatment for stage IV breast cancer, local and regional treatments such as surgery, radiation therapy, or regional chemotherapy are sometimes used as well. These can help treat breast cancer in a specific part of the body, but they are very unlikely to get rid of all of the cancer. These treatments are more likely to be used to help prevent or treat symptoms or complications from the cancer.
Radiation therapy and/or surgery may also be used in certain situations, such as:
- When the breast tumor is causing an open wound in the breast
- To treat a small number of metastases in a certain area, such as the brain
- To help prevent bone fractures
- When an area of cancer spread is pressing on the spinal cord
- To treat a blood vessel blockage in the liver
- To provide relief of pain or other symptoms
In some cases, regional chemo may be useful as well.
If your doctor recommends such local or regional treatments, it is important that you understand their goalwhether it is to try to cure the cancer or to prevent or treat symptoms.
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Treatment Of Breast Cancer In Men By Stage
This information is based on AJCC Staging systems prior to 2018 which were primarily based on tumor size and lymph node status. Since the updated staging system for breast cancer now also includes the ER, PR and HER2 status, the stages may be higher or lower than previous staging systems. Whether or not treatment strategies will change with this new staging system are yet to be determined. You should discuss your stage and treatment options with your physician.
Because there have been few clinical trials on treatment of male breast cancer, most doctors base their treatment recommendations on their experience with the disease and on the results of studies of breast cancer in women. With some minor variations, breast cancer in men is treated the same way as breast cancer in women.
The stage of your breast cancer is an important factor in making decisions about your treatment options. In general, the more the breast cancer has spread, the more treatment you will likely need. But other factors can also be important, such as:
- If the cancer cells contain hormone receptors
- If the cancer cells have large amounts of the HER2 protein
- Your overall health and personal preferences
- How fast the cancer is growing
Talk with your doctor about how these factors can affect your treatment options.
How Can I Prevent Breast Cancer Recurrence
Healthcare providers dont know why some people experience breast cancer recurrence. A recurrence isnt your fault. You didnt do anything wrong to cause it or fail to do something more to prevent it.
Certain medications may reduce the risk of breast cancer recurrence in people who have early stage breast cancer. For estrogen-receptive breast cancer, hormonal therapies including tamoxifen or aromatase inhibitors block either the activity of estrogen or the bodys production of estrogen. Chemotherapy may also be recommended to reduce risk of breast cancer recurrence.
Early diagnosis may make it easier to treat a recurrence. Follow your healthcare providers recommendations for mammograms and other screenings. You should also perform regular breast self-exams. Get familiar with how your breasts look and feel so you can see your provider quickly if you notice changes. And remember that most breast changes occur for reasons other than cancer.
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How Bone Metastasis Is Treated
Bone metastases are treated with the same treatments used to treat the primary cancer. For instance, metastatic prostate cancer in the bone may be treated with hormone therapy. Along with treatment for the primary cancer, these treatments can be used for bone metastasis:
Radiation therapy and radiopharmaceuticals
Other treatments, including physical therapy and pain medicines
Symptoms If Cancer Has Spread To The Bones
You may have any of these symptoms if your cancer has spread to the bones:
- an ache or pain in the affected bone
- breaks in the bones because they are weaker
- breathlessness, looking pale, bruising and bleeding due to low levels of blood cells blood cells are made in the bone marrow and can be crowded out by the cancer cells
Sometimes when bones are damaged by advanced cancer, the bones release calcium into the blood. This is called hypercalcaemia and can cause various symptoms such as:
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Can Earlier Detection Of Recurrence Improve Breast Cancer Outcomes
The risk of metastatic relapse weighs heavily on the minds of patients, physicians and caregivers for years, sometimes decades, after treatment of the primary tumour is complete. Nearly 17 million cancer survivors are living in the United States, 3.9 million of whom are breast cancer survivors, and repeated monitoring for cancer recurrence in these individuals presents a significant challenge to healthcare delivery systems. For breast cancer patients, current American Society of Clinical Oncology and National Comprehensive Cancer Network guidelines limit follow-up care to mammography, medical history and physical exam, stating that in the absence of clinical signs and symptoms suggestive of recurrent disease, there is no indication for laboratory or imaging studies for metastases screening.,Despite these guidelines, however, many patients receive high-cost imaging analysis and tumour marker blood tests during routine follow-up exams, exposing them to radiation and increasing healthcare costs.,,, So, what has led to the current precarious balance between the desire to detect recurrence early and clinical guidelines that limit the use of diagnostic tests?
Table 1 Exploiting tumour dormancy as a window of therapeutic opportunity to target MRD.
What Are Bone Metastases
Bone metastases are not the same as cancer that starts in the bone. Cancer that starts in the bone is called primary bone cancer. There are different types of primary bone cancers, like osteosarcoma and Ewing sarcoma.
A tumor that has metastasized to bone is not made of bone cells. Bone metastases are made up of abnormal cancer cells that started from the original tumor site. For instance, lung cancer that spreads to the bone is made of lung cancer cells. In this case, the bone metastasis would be called metastatic lung cancer. In adults, metastatic bone cancer is much more common than primary bone cancer.
Cancer cells that spread to the bone often affect these places:
Cancer cells that spread from tumors in other parts of the body can form two main types of bone tumors:
The tumor may eat away areas of bone. This creates holes called osteolytic lesions. They can make bones fragile and weak. So the bones can break or fracture easily. These areas may be painful.
The tumor may cause the bone to form and build up abnormally. These areas of new bone are called osteosclerotic or osteoblastic lesions. They’re hard, but they’re weak and unstable. They may break or collapse. They can also be painful.
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Outlook Once Cancer Has Spread To The Bones
The research on cancer metastasis is rapidly growing. As researchers better understand the mechanisms of bone metastasis, new drugs and other treatments are being developed. These target particular processes in cells involved in how the cancer cells invade and grow in bones.
The use of nanoparticles to deliver drugs is very encouraging. These tiny particles are able to deliver drugs to the bone with minimal toxicity to the person with cancer.
Rapidly treating bone metastasis can lead to a
Bone Weakening And Fracture
Secondary breast cancer in the bone may mean the affected bones are weakened, which can increase the risk of a fracture.
If a bone has fractured you may need surgery to try to repair the fracture. You may also be given drug treatment to stop this happening in the future. You may have radiotherapy after the surgery.
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Breast Subtypes And Prognosis Of Breast Cancer Patients With Initial Bone Metastasis: A Population
- Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
Background: Metastatic breast cancer is a highly heterogeneous disease and bone is one of the most common metastatic sites. This retrospective study was conducted to investigate the clinical features, prognostic factors and benefits of surgery of breast cancer patients with initial bone metastases.
Methods: From 2010 to 2015, 6,860 breast cancer patients diagnosed with initial bone metastasis were analyzed from Surveillance, Epidemiology, and End Results database. Univariate and Multivariable analysis were used to identify prognostic factors. A nomogram was performed based on the factors selected from cox regression result. Survival curves were plotted according to different subtypes, metastatic burdens and risk groups differentiated by nomogram.
Our study has provided population-based prognostic analysis in patients with initial bone metastatic breast cancer and constructed a predicting nomogram with good accuracy. The finding of potential benefit of surgery to overall survival will cast some lights on the treatment tactics of this group of patients.