Effect Of Hormonal Changes On Breasts
As women develop from pre-puberty through puberty, pregnancy and to menopause, the breasts will be affected by a variety of fluctuations in hormones.
During puberty, hormones produced by the ovaries cause growth and development of the breast. After puberty, the hormones oestrogen and progesterone will change throughout a womans monthly menstrual cycle. This may cause women to have swollen or tender breasts at different times of the month.
During pregnancy the body will produce additional oestrogen and progesterone, which trigger further growth and development of the breast to prepare mothers for breastfeeding.
Around the time of menopause , the ovaries stop producing female hormones including oestrogen. Without oestrogen, the breast tissue decreases in size. After menopause , monthly menstrual periods stop.
How Is A Local Recurrence Or Metastasis Found
Breast cancer can recur at the original site . It can also return and spread to other parts of the body .
Local recurrence is usually found on a mammogram, during a physical exam by a health care provider or when you notice a change in or around the breast or underarm.
Metastasis is usually found when symptoms are reported to a provider.
If you have a local recurrence or metastasis, its not your fault. You did nothing to cause it.
Learn about follow-up care after breast cancer treatment.
What Is Stage Iv Breast Cancer
Stage IV is the most advanced stage of breast cancer. It has spread to nearby lymph nodes and to distant parts of the body beyond the breast. This means it possibly involves your organs such as the lungs, liver, or brain or your bones.
Breast cancer may be stage IV when it is first diagnosed, or it can be a recurrence of a previous breast cancer that has spread.
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What Is Metastatic Cancer
In metastasis, cancer cells break away from where they first formed , travel through the blood or lymph system, and form new tumors in other parts of the body. The metastatic tumor is the same type of cancer as the primary tumor.
Cancer that spreads from where it started to a distant part of the body is called metastatic cancer. For many types of cancer, it is also called stage IV cancer. The process by which cancer cells spread to other parts of the body is called metastasis.
When observed under a microscope and tested in other ways, metastatic cancer cells have features like that of the primary cancer and not like the cells in the place where the metastatic cancer is found. This is how doctors can tell that it is cancer that has spread from another part of the body.
Metastatic cancer has the same name as the primary cancer. For example, breast cancer that spreads to the lung is called metastatic breast cancer, not lung cancer. It is treated as stage IV breast cancer, not as lung cancer.
Sometimes when people are diagnosed with metastatic cancer, doctors cannot tell where it started. This type of cancer is called cancer of unknown primary origin, or CUP. See the Carcinoma of Unknown Primary page for more information.
Risk Factors And Epidemiologic Features
In addition to a distinct molecular and pathologic profile, the epidemiology and risk factors associated with triple-negative breast cancer are distinct, especially when compared with endocrine-sensitive luminal breast tumors. The Carolina Breast Cancer Study, a population-based, case-control study aimed at determining clinical associations and distributions across distinct breast cancer subtypes, has refined our understanding of the epidemiologic and risk factors associated with triple-negative breast cancer. In the initial study of women diagnosed with invasive breast cancer, the prevalence of breast cancer subtypes within racial and menopausal subsets were determined. Immunohistochemical staining was used to classify specific subtypes in approximately 500 tumors, and basal-like tumors were defined as triple negative and cytokeratin 5/6 positive and/or HER1 positive. Results indicated that those with basal-like tumors were more likely to be African American compared with nonAfrican American and premenopausal compared with postmenopausal . There was a particularly high prevalence of basal-like tumors among premenopausal African American women compared with postmenopausal African American women and nonAfrican American women of any age . The observation that triple-negative breast cancers more commonly arise in younger African American women has been confirmed in several additional studies, although the exact cause for this association is not yet fully understood.,
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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.
Stages Of Breast Cancer And What They Mean
Breast cancer stages are usually expressed on a scale of 0 to 4.
Stage 0 is considered non-invasive breast cancer, with no evidence that the cancer has spread beyond the part of the breast where it began to grow, including to nearby lymph nodes.
Stages 1 to 3 generally describe breast cancer that may have spread to other parts of the breast and nearby lymph nodes, with stages increasing with the size of tumors and extent of spread.
Cancer that remains localized to the breasts is the most treatable.
Breast cancer tumors can grow directly from breast tissue to other nearby locations, such as the chest wall or the skin of the breast. This is considered stage 3 breast cancer.
Stage 4 is metastatic breast cancer , meaning that cancer that originated in the breast has now spread to other parts of the body.
In stage 4 breast cancer, cancer cells can spread beyond the breasts by invading lymph nodes near the breast and traveling to other parts of the body via the lymphatic system.
Cancer cells also can move through the bloodstream to inhabit other organs and regions of the body.
The most common destinations for MBC or advanced breast cancer cells are the brain, bones, lungs, and liver.
The outcome for Stage 4 breast cancer that has metastasized, or spread to distant organs of the body, is considerably lower than for earlier stages, with a 28 percent 5-year survival rate.
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What Is A Breast Cancer Recurrence
Breast cancer recurrence means that the cancer was diagnosed when limited to the breast and/or armpit lymph nodes, then treated, and at some time later has come back.
This can occur in several ways:
- Local and/or regional recurrence: the breast cancer that was previously treated returns within the breast, chest wall or regional lymph nodes.
- New primary breast cancer: an unrelated new breast cancer occurs in one or the other breast. This actually isnt a local recurrence at allits a new cancer in the breast . This typically occurs many years after the original cancer and in an entirely different area of the breast. Its pathology is often different lobular instead of ductal, for example. Though they are often counted as recurrences in the statistics for breast conservation, they should be treated as completely new cancers, much as with new cancers in the opposite breast.
- Distant or systemic recurrence or metastasis is much more serious than local recurrence and is synonymous with stage 4 disease. For breast cancer patients, the most common areas of spread are the bone, liver, lungs and brain
Breast cancer recurrence occurs if:
- Cells from the original breast cancer diagnosis break away and hide nearby in the breast or spread elsewhere in the body
- Treatment, including surgery, chemotherapy, radiotherapy and/or hormone therapy have not gotten rid of all these cancer cells from the body.
The Sentinel Lymph Node
When cancer spreads, the lymph node located closest to the original tumor is usually affected first. In breast cancer cases, the sentinel lymph node is often located in the underarm area. An important part of the bodys immune system, lymph nodes are small structures that fight infection by attacking and destroying harmful substances carried in the lymphatic fluid. As a tumor drains into the sentinel lymph node, the immune system works hard to filter and destroy the cancerous cells, but the cancer may become trapped within the node.
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Can Breast Cancer Be Prevented
A lot of breast cancers are detected at an early stage, by breast screening. However, a small number are not. Some women may have developed breast cancer before they have their first mammogram and some may develop breast cancer between mammograms. All women of every age should be breast aware. That is, get to know how your breasts and nipples normally look and feel. Try to recognise any changes that occur before and after your periods. See your GP if you notice any changes, lumps, or other abnormalities in your breasts or nipples. Don’t wait until your next scheduled screening appointment.
There is some evidence that regular exercise may reduce your risk of breast cancer by as much as a third. If you have been through the menopause, it is particularly important you are not overweight or obese. This is because being overweight causes more oestrogen to be produced, which can increase the risk of breast cancer.
Studies have shown that women who breast-feed their children are less likely to develop breast cancer than those who do not. The most likely reason for this is that women do not produce an egg as regularly while they are breast-feeding and oestrogen levels remain stable.
Local Recurrence After Mastectomy
Even though the entire breast is removed in a mastectomy, breast cancer can still return to the chest area. If you notice any changes around the mastectomy scar, tell your health care provider.
The more lymph nodes with cancer at the time of the mastectomy, the higher the chances of breast cancer recurrence.
Local recurrence after a mastectomy is usually treated with surgery, and radiation therapy if radiation therapy wasnt part of the initial treatment.
Treatment may also include chemotherapy, hormone therapy and/or HER2-targeted therapy.
Box 1 How Rapid Autopsy Studies Can Inform On Metastatic Dissemination And Relapse
Rapid autopsy: rapid post-mortem collection, examination and biobanking of tissuesfresh, snap-frozen and fixedfrom deceased patients shortly after death.
Rapid autopsy cancer programme: coordinated effort among oncologists, pathologists and scientists aimed at collecting specimens from cancer patients within a post-mortem interval of 68h before key biological information within the tissues of interest is lost.
Multiregional biopsies: to conduct extensive, spatial sampling of tissuesprimary and metastatic, cancerous and normalfor in-depth, high-resolution multi-omics analysis.
Physiological model: to analyse DTCs in their natural metastatic niche.
to generate novel, ex vivo living patient-derived modelsautopsy-derived xenografts and organoids of metastatic tumours from sites that would otherwise be difficult to sample for functional evaluation .
Cancer evolution: to study the phylogenetic relationship of each sampled site to each other and infer the complete clonal evolution of a neoplasm.
Dormancy: to examine why some DTCs lodged in certain organs of the human body become dormant for years to decades.
Drug resistance: to study why DTC spread across different sites responds differently to therapy, with some developing resistance and others remaining sensitive to treatment.
Recurrence: to understand why only some DTCs residing in certain sites of the human body give rise to active metastases, ultimately responsible for patients relapse.
Who Is At Risk Of Breast Cancer Recurrence
Everyone who has received a breast cancer diagnosis is at risk of recurrence, however the risk differs markedly depending on a number of factors listed below. Some breast cancers, when diagnosed very early when small and without lymph node involvement, have an excellent prognosis and are very unlikely to recur. On the contrary, larger cancers, with lymph node involvement or with a more invasive behaviour, are unfortunately at a higher risk of recurrence.
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Treating Metastatic Breast Cancer
There isnt a cure for metastatic breast cancer. There are treatments aimed at preventing further progression, reducing symptoms, and improving the quality and length of life. Treatments are individualized.
They depend on the type and extent of recurrence, the type of cancer, previous treatment received, and your overall health. Treatment options may include:
- hormone therapy for estrogen receptor-positive breast cancer, which is the most common type of breast cancer
- medications that target specific proteins on cancer cells to stop growth, sometimes called targeted therapy
- bone-building drugs to reduce bone pain and increase bone strength
- radiation therapy
The US Food and Drug Administration approved the drug palbociclib in 2015 for use in conjunction with an aromatase inhibitor. This combination is used to treat ER-positive, HER2-negative metastatic breast cancer in postmenopausal women.
Other therapies used in hormone-positive breast cancer include:
- selective estrogen receptor modulators
How The Cancer Spreads
Its unclear exactly why cancer cells multiply and spread to other parts of the body. All cells have DNA, which is the material that carries all the genetic information about a living thing.
When the DNA in a normal cell is damaged, the cell can sometimes repair itself. If the cell doesnt repair itself, it dies.
Cancer cells are abnormal in that they dont die or repair themselves when their DNA is damaged. The damaged cells just keep on multiplying, replacing healthy tissue.
With breast cancer, a malignant tumor, or collection of cancer cells, forms in the breast.
If the cancer is diagnosed and treated early, the cancer cells may never spread. If its not diagnosed and treated early, theres a chance the cancer can show up somewhere else in your body.
Cancer cells can travel through the bloodstream and the lymphatic system to anywhere in the body. So cancer cells from a tumor in the breast can invade the bloodstream and collect in any organ.
If cancer cells that have migrated from the breast appear in the pancreas , the cancer is referred to as a breast cancer metastasis.
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Noninvasive Or Preinvasive Breast Cancers
Noninvasive cancers remain confined to the primary site of development, but are always treated, because it is not possible to know if they will become invasive or not. Noninvasive breast cancers include:
- Ductal carcinoma in situ : Abnormal cells in the milk duct
- Lobular carcinoma in situ : Abnormal cells in the lobules
Study Shows Different Types Of Cancers Likely To Spread To Specific Areas Of The Brain
Brain metastasis occurs when cancer in one part of the body spreads to the brain. The lifetime incidence of such metastatic brain tumors in cancer patients is between 20%-45%, research shows.
A new study from USC Norris Comprehensive Cancer Center, part of Keck Medicine of USC, suggests that the region cancer spreads to in the brain may not be random, but rather, is dependent on where the cancer originated in the body.
“We discovered that different types of cancer are more likely to show up in specific parts of the brain once they metastasize, indicating the location of tumors follow a distinct pattern,” said Gabriel Zada, MD, a brain and tumor neurosurgeon with Keck Medicine of USC and senior author of the study. He is also a member of USC Norris and director of the USC Brain Tumor Center.
Zada and colleagues analyzed the location of brain tumors caused by five common types of cancermelanoma , lung, breast, renal and colorectal. They discovered that lung cancer and melanoma showed a higher likelihood for the metastasis to be at the frontal and temporal lobes . Breast, renal and colon cancers had a higher propensity to spread to the back of the brain, such as the cerebellum and brainstem.
The findings are important not only because they may predict where a specific cancer may spread in the brain, but because they also have implications for how brain tumors grow.
The study was published in the Journal of Neurosurgery.
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What Is Metastatic Breast Cancer
The spread of breast cancer to other parts of the body is called metastasis. Its not uncommon. About 20 to 30 percent of all breast cancers will become metastatic.
Metastatic breast cancer is also known as stage 4 breast cancer. This means that cancer cells have spread in the body beyond the original site of diagnosis.
Cancer can spread through the lymphatic system or through the blood. This allows the cancer to travel to other organs. The most common organs that breast cancer cells travel to are the:
Breast cancer, like all cancers, is categorized by stages. The location, size, and type of tumor determine the cancers stage.
Stage 4 is the most serious and the most complicated to treat because the cancer has spread beyond its original location.
Stage 1 breast cancer is highly treatable because cancer cells are still isolated in the breast. Stages 2 and 3 are progressively more serious.
The pancreas is located near the stomach. It has two main jobs.
First, it releases fluid into the small intestine to help with digestion.
Second, the pancreas is responsible for the production of important hormones. This includes insulin, which helps manage blood sugar levels in the body.
If cancer develops in the pancreas, it may be a while before you notice any symptoms. Often the first symptom is jaundice, a yellowing of the skin. Liver problems can also lead to jaundice.
Other symptoms of cancer in the pancreas include: