Prof. Yusuf Yıldırım

CAUSES & RISK FACTORS

Breast cancer, like other cancers, occurs when the growth and reproduction of cells starts to get out of control. This type of cancer occurs almost exclusively in women, but rarely men can also develop breast cancer. Most breast cancers are carcinomas of epithelial origin, usually adenocarcinomas that start from cells in the ducts (ductal) that carry milk to the nipple or from cells in the lobules/glands (lobular) responsible for milk production. Breast cancer can be either non-invasive (in situ) or invasive (infiltrative). The term invasive breast cancer is used to describe any breast cancer that invades the surrounding breast tissue and blood or lymph vessels. This type of breast cancer accounts for the vast majority (85 per cent) of breast cancers and unless otherwise stated, invasive breast cancer is referred to as breast cancer (Invasive Ductal Carcinoma-IDC, Invasive Lobular Carcinoma-ILC or mixed IDC/ILC). Non-invasive (in situ) breast cancer (DCIS) accounts for a smaller proportion of breast cancers and does not spread (metastasize) to other parts of the body via lymph or blood unless it has an invasive component.

There is also a molecular classification of breast cancer, which is very important in guiding treatment and predicting prognosis. This classification is based on the detection of estrogen and/or progesterone hormone receptors (ER and/or PR), overexpression of HER2 oncoprotein and Ki-67, a cell proliferation marker, in tumor cells:

• Luminal A (55%): hormone positive, HER2 negative               
• Luminal B (20%): hormone positive, HER2 negative/positive  
• HER2-enriched (non-luminal HER2 positive) (10%)
• Basal-like (Triple-negative) (15%).         

Regardless of histological and molecular classification, there are two specific types of breast cancer. These are:

• Inflammatory Breast Cancer (IBC)
• Paget's Disease of The Breast.

Overall, the average risk of a woman developing breast cancer at some point in her life is about 13 per cent. This means that the chance of developing breast cancer is 1 in 8. This cancer occurs mostly in middle-aged and older women (average age 62). Although rare under the age of 40, breast cancers can also be seen in people in their twenties who are genetically predisposed.

Breast cancer is a complex disease influenced by numerous risk factors. Understanding these factors is crucial for both prevention strategies and early detection initiatives. Each of the risk factors can affect your risk to a different degree, and most women with one or more of these risk factors will never develop breast cancer. Risk factors associated with breast cancer include:

• Genetic factors: Genetics plays a very important role in the risk of breast cancer. In particular, certain inherited mutations in the BRCA1 and BRCA2 genes significantly increase the risk of developing breast cancer.
• Having a personal history of breast cancer
• Advanced age
• Race and ethnicity
• Reproductive factors
• Hormone replacement therapy (HRT)
• Exposure to DES (diethylstilbestrol)
• Having dense breast tissue
• Having certain benign (non-cancerous) breast conditions
• Environmental factors
• Lifestyle choices
• Other (weak, unclear or controversial) risk factors: Diet, hormonal contraceptives, breast implants, being taller, smoking, night shift work etc.

In conclusion, breast cancer risk is influenced by a combination of genetic, hormonal, lifestyle and environmental factors. Understanding these multifaceted influences is crucial for developing comprehensive prevention and early detection strategies.

SYMPTOMS, DIAGNOSIS & STAGES

The signs of breast cancer can vary, but common signs include:

• Lump or mass
• Changes in breast size or shape
• Changes in the nipple
• Pain
• Swollen lymph nodes. 

Many of these symptoms can also be caused by benign (non-cancerous) breast conditions. Nevertheless, it is important that any new breast lump, swelling or other change is checked by a specialist so that the cause can be found and treated if necessary. 

During a physical examination (also called clinical breast examination-CBE) for breast cancer, your doctor will do the following:

• Visual examination of the breast
• Palpation of lumps or masses
• Lymph node examination.

Imaging tests play a vital role in the diagnosis of breast cancer. Common imaging modalities include:

• Mammography
• Ultrasound
• Magnetic Resonance Imaging (MRI).

A biopsy is the definitive method for confirming or excluding breast cancer. There are different types of breast biopsies. Some are performed using a hollow needle (fine needle aspiration biopsy or core needle/tru-cut biopsy), others using an incision in the skin (open/surgical biopsy). Although needle biopsy can often be performed instead of surgical biopsy, the selected method depends on the following factors:

• How suspicious the breast change looks or feels,
• The size of the mass and whether it can be well localized (by palpation and/or ultrasound examination),
• Where the mass is located in the breast,
• Whether there is more than one suspicious area,
• General health,
• Personal preferences.

If the change in the breast can be felt, the surgeon can perform the biopsy using the sense of touch as a guide. However, if the change cannot be felt and/or is difficult to find, an imaging test such as a mammogram, ultrasound or MRI may be performed before surgery to help place a wire or other localization device (such as a radioactive or magnetic seed or radiofrequency reflector) in the suspicious area. This helps guide the surgeon to the right spot. This is called a "pre-operative localization study" and includes wire/needle localization and newer methods of localization.

The lymph nodes in the armpit may be biopsied to check for cancer spread (lymph node biopsy). This type of biopsy may be needed before deciding on the treatment of breast cancer. Checking of lymph nodes is often done with fine needle aspiration biopsy (FNAB) or core needle biopsy, depending on the situation.

Breast cancer cells produce substances called tumor markers, which can sometimes be found in the blood. Although blood tests for these tumor markers can be useful in detecting breast cancer that has spread to other organs, they are not used alone to diagnose or monitor breast cancer. These include:

• CA 15-3 (Cancer antigen 15-3)
• CA 27-29 (Cancer antigen 27-29)
• CEA (Carcinoembryonic antigen).

Along with the diagnosis of cancer, the presence of certain proteins in tumor cells is also investigated. These are:

• Ki-67 (cell proliferation) test
• Hormone receptors: Estrogen receptor (ER) and progesterone receptor (PR).
• HER2
• PD-L1.

In some cases, doctors may test for certain gene mutations (changes) in breast cancer cells. This is to investigate whether certain targeted drugs or immunotherapy drugs can help treat advanced cancer. Some genetic tests have a role in determining prognosis and whether adjuvant treatment is needed in early-stage disease (gene expression tests). These molecular tests can be performed on tissue taken during biopsy or surgery. If the biopsy sample is too small and not all molecular tests can be performed, blood can also be tested (liquid biopsy). Specific gene mutations mostly used in breast cancer include:

• BRCA1 and BRCA2 mutations
• PIK3CA gene mutation
• ESR1 gene mutations
• NTRK fusion genes
• MSI and MMR testing
• Tumor mutation burden (TMB)
• Gene expression testing/profiling: The most used gene expression test today is The Oncotype DX test. Other commonly used gene expression tests are MammaPrint, Prosigna and Breast Cancer Index tests.

Stages of breast cancer range from 0 to IV and the higher the stage, the worse the prognosis (chance of survival). The simplest description of breast cancer stages is as follows:

• Stage 0 (Ductal carcinoma in situ-DCIS*): Non-invasive breast cancer (pre-cancerous change)
• Stage I (Early breast cancer): The cancer in the breast is still fairly small (2cm or smaller), and either have not spread to the lymph nodes or have spread to only a tiny area in the sentinel lymph node in the armpit (microscopic involvement).
• Stage II (Early breast cancer): The cancer is larger than in stage I (but does not exceed 5 cm) and/or is found in just a few nearby lymph nodes.
• Stage III (Locally advanced breast cancer): The cancer is larger than in stage II (>5 cm), or involves the skin of the breast or the chest wall, or is a type of breast cancer called inflammatory breast cancer, and/or has spread from the breast to more than just a few regional lymph nodes.
• Stage IV (Metastatic breast cancer): The cancer has spread to other parts of your body (including distant lymph nodes).

* Non-invasive breast cancer (Ductal carcinoma in situ: DCIS) is discussed separately.

TREATMENT & PROGNOSIS

The stage of breast cancer is an important factor in deciding treatment options. However, other factors listed below may also be significant and can be taken into account:

• Whether cancer cells have hormone receptors.
• The presence or absence of excess HER2 protein in cancer cells.
• How fast the cancer is growing (measured by grade or Ki-67).
• Whether a specific targetable gene mutation is detected in cancer cells.
• Whether the cancer has affected important organs such as the lungs or liver.
• Whether you're going through menopause.
• Your general state of health and personal preferences.

Treating Stage I Breast Cancer

The main treatment for stage I breast cancer is surgery. These cancers can be treated with breast-conserving surgery (BCS; sometimes called lumpectomy or partial mastectomy) or (total) mastectomy. Nearby lymph nodes will also need to be checked by sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND). Some women may have breast reconstruction at the same time as cancer removal surgery. However, if a patient needs radiation therapy after surgery, it is advised to wait for reconstruction procedure until the completion of radiotherapy. You are less likely to need radiation therapy if you have had a (total) mastectomy, but this treatment may be given depending on the cancer details. If BCS is performed, radiation therapy is usually given after surgery to reduce the chance of cancer recurrence in the breast. As an exception, women aged 65 years and older may not be given radiation therapy after BCS if they have ALL of the criteria listed below (adjuvant radiation therapy for women with these characteristics reduces the likelihood of cancer recurrence, but there is no evidence that it prolongs survival):

• The tumor is 3 cm or less in diameter and removed with adequate margin.
• None of the removed lymph nodes are cancer-free.
• The cancer has ER or PR receptors (hormone therapy will be given).

If a woman has hormone receptor-positive (ER-positive or PR-positive) breast cancer, regardless of tumor size, most doctors will recommend hormone therapy (Tamoxifen or aromatase inhibitor or one followed by the other) as adjuvant treatment after surgery. Hormone therapy is usually given for at least 5 years. If the tumor is larger than 0.5 cm in diameter, postoperative chemotherapy (adjuvant chemotherapy) is sometimes recommended. The age at diagnosis can help to decide whether chemotherapy should be offered. Some doctors may also offer chemotherapy for smaller tumors, especially if they have unfavorable features (a fast-growing cancer: high Ki67 index, hormone receptor negative, HER2 positive; or a high score on a gene panel such as Oncotype DX). Many women with HER2 positive cancer will be treated with neoadjuvant (before surgery) chemo and Trastuzumab (with or without Pertuzumab) for up to 1 year, followed by surgery and more Trastuzumab (±Pertuzumab). If residual cancer is found during surgery after neoadjuvant treatment, Trastuzumab may be replaced with a different medicine called Ado-trastuzumab emtansine, given as 14 doses every 3 weeks. Women with BRCA mutation and hormone-positive, HER2-negative breast cancer may be given the targeted drug Olaparib after surgery (usually for one year).

Treating Stage II Breast Cancer

Stage II cancers, like stage I cancers, are treated with either breast-conserving surgery (BCS; sometimes called lumpectomy or partial mastectomy) or (total) mastectomy. Nearby lymph nodes will also be checked by sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND). Women who have undergone BCS are treated with radiation therapy after surgery.  Women who have had a total mastectomy are usually treated with radiation if the cancer is found in the lymph nodes. Some patients who exhibit cancer in only a few lymph nodes on SLNB may not undergo the removal of their remaining lymph nodes to ascertain the presence of additional cancer. In such cases, the potential benefits of radiation therapy following mastectomy may be discussed. If a patient initially diagnosed with stage II breast cancer was treated with a systemic therapy, such as chemotherapy or hormone therapy, prior to surgery, radiation therapy may be recommended if cancer is found in the lymph nodes during the mastectomy. If chemotherapy is also needed after surgery, radiation will be postponed until the completion of chemotherapy. In some women, breast reconstruction can be done while cancer removal operation is taking place. However, if a patient needs radiation after surgery, it is better to wait for reconstruction until the radiation is complete.

Systemic treatment is recommended for most women with stage II breast cancer. Systemic treatments are given before surgery (neoadjuvant treatment) in some women and after surgery (adjuvant treatment) in others. In certain cases, treatment starts before surgery and continues after surgery. Neoadjuvant treatment is a viable option for women with large tumors, as it can effectively reduce the tumor size prior to surgery. This may potentially render BCS a viable surgical option. Neoadjuvant treatment is also a preferable option for women with triple-negative breast cancer (TNBC) or HER2-positive breast cancer, as the treatment for these patients after surgery is typically selected based on the extent of residual cancer in the breast and/or lymph nodes at the time of surgery. 

A gene panel test such as Oncotype DX can be performed on the tumor sample to decide which women with stage II hormone receptor-positive, HER2-negative breast cancer would benefit from adjuvant chemotherapy.

Systemic treatments (drugs) used in stage II breast cancer will depend on the woman's menopausal status and the results of tumor testing (pathology and gene panel). If the cancer is hormone receptor positive, hormone therapy (Tamoxifen, an aromatase inhibitor (AI) or one or the other) is usually used. It can be started before the operation, but it must also be given after the operation as it continues for at least 5 years. Chemotherapy can be given before and/or after surgery. Many women with HER2-positive cancer will be treated first (neoadjuvant) with Trastuzumab (with or without Pertuzumab), followed by surgery and then further withTrastuzumab (±Pertuzumab) for up to one year. If residual cancer is found during surgery after neoadjuvant treatment, the targeted drug Ado-trastuzumab emtansine may be used instead of Trastuzumab (given as 14 doses every 3 weeks). For women with hormone receptor positive cancer in the lymph nodes, after completing 1 year of Trastuzumab treatment, additional treatment with an oral targeted drug called Neratinib for 1 year may be recommended. Women with hormone receptor-positive, HER2-negative, early-stage breast cancer with cancer in the lymph nodes and a high chance of recurrence may be given the targeted drug Abemaciclib after surgery (in combination with Tamoxifen or an AI). It is usually a pill given twice a day for 2 years. Women with a BRCA mutation and a hormone receptor-positive, HER2-negative tumor who still have cancer in the tissue removed by surgery after neoadjuvant chemotherapy can be given the targeted drug Olaparib for one year. Women with TNBC can be given the immunotherapy drug Pembrolizumab before and after (or both before and after) surgery. 

Treating Stage III Breast Cancer

In stage III breast cancer, the tumor is larger than 5 cm or has invaded the breast skin or the muscle under the breast, or the cancer has spread to many regional lymph nodes. There are two main approaches to the treatment of breast cancer at this stage:

Starting with neoadjuvant treatment

Most of the time these cancers are treated with neoadjuvant (pre-operative) chemotherapy. Neoadjuvant treatment is based on hormone receptor (HR) and HER2 status. Preoperative systemic therapy has the following benefits:

o    It can preserve the breast by shrinking tumor.

o    It provides important information about tumor responds to treatment. This is very useful in TNBC and HER2 positive breast cancers.

o    It is beneficial to select adjuvant treatment regimens that are suitable for patients diagnosed with HER2-positive and TNBC, who have residual tumors.

o    Allow time for genetic testing.

o    Allow time to plan breast reconstruction in women who prefer mastectomy 

o    Allow less lymph nodes to be removed during surgery.

o    Allow time for you to decide about and prepare for surgery.

For HER2-positive tumors, the targeted drug Trastuzumab (Herceptin®) is also often given in combination with Pertuzumab (Perjeta®). This can shrink the tumor enough for breast-conserving surgery (BCS). In the event that the tumor does not demonstrate sufficient shrinkage, a total mastectomy is performed. The nearby lymph nodes must also be assessed. Sentinel lymph node biopsy (SLNB) is typically not an option for stage III cancers, and thus axillary lymph node dissection (ALND) is usually performed. If preoperative systemic treatment does not result in sufficient tumor shrinkage (enough to be surgically removed), the patient will receive further systemic treatment and/or radiation therapy (RT). If the tumor shrinks sufficiently, surgery (followed by systemic therapy and RT) is performed. Neoadjuvant treatment is a preferable option for women with stage III TNBC or HER2-positive breast cancer, as the subsequent treatment is selected based on the extent of residual disease in the breast and/or lymph nodes at the time of surgery. Women with TNBC may be administered the immunotherapy drug Pembrolizumab prior to and following surgery. RT is often needed after surgery. If breast reconstruction is planned, it is usually postponed until after the radiation treatment. For some, additional chemotherapy is also given after the operation. After surgery, some women with HER2 positive cancer will be treated with Trastuzumab (with or without Pertuzumab) for up to one year. Many women with HER2-positive cancer will be treated with Trastuzumab (±Pertuzumab) first, followed by surgery and then more Trastuzumab (±Pertuzumab) for up to one year. Ado-trastuzumab emtansine may be used instead of Trastuzumab if any residual cancer is found at the time of surgery after neoadjuvant treatment (given as 14 doses every 3 weeks). For women with hormone receptor positive cancer in the lymph nodes who have completed one year of Trastuzumab treatment, additional treatment with an oral targeted medicine called Neratinib for one year may be recommended. Women with hormone receptor-positive (ER-positive or PR-positive) breast cancer will also receive adjuvant hormone therapy, which can often be taken at the same time as Trastuzumab. Women with hormone receptor-positive and HER-negative cancer in their lymph nodes may be given Abemaciclib in combination with Tamoxifen or an AI after surgery. This is usually a pill given twice a day for 2 years. Women with BRCA mutation and hormone receptor-positive, HER2-negative breast cancer who still have cancer in tissue removed by surgery after neoadjuvant chemotherapy may be given the targeted drug Olaparib for one year to reduce the chance of recurrent cancer.

Starting with surgery

For some women with stage III cancer, "surgery first" may be an option. Since these tumors are quite large and/or have grown into nearby tissues, this usually means a (total) mastectomy. For women with large breasts, BCS may be an option if the cancer has not spread to nearby tissues. SLNB may be an option for some patients, but most will need ALND. Surgery is usually followed by adjuvant chemotherapy and/or hormone therapy and/or targeted drug therapy and/or HER2 positive therapy (Trastuzumab, Pertuzumab or Neratinib) depending on the characteristics of the cancer cells. Radiation is recommended after surgery.

Treating Stage IV (Metastatic) Breast Cancer

Stage IV cancers have spread to other parts of the body, i.e. metastasised. The most common sites of metastasis in breast cancer are the bones, liver, and lungs. It can also spread to the brain or other organs. Systemic drug therapies are the main treatment for women with stage IV breast cancer. In some cases, local or regional treatments (surgery and/or radiation therapy) may be useful. Treatment to relieve symptoms (supportive care) is also important for these patients.

Systemic (drug) treatments

Systemic drug therapies may include one or a combination of several of these: Hormone therapy, Chemotherapy, Targeted drugs, and Immunotherapy. Treatment can often shrink tumors (or slow their growth), improve symptoms and help some women live longer. Systemic treatment usually continues until the cancer starts to grow again or the side effects become unacceptable. Several medicines can be tried if necessary. As current treatments are unlikely to fully cure metastatic breast cancer, there is also the option for eligible patients to take part in a clinical trial testing a newer treatment. The types of drugs used for stage IV breast cancer depend on the hormone receptor status, the HER2 status of the cancer, and sometimes the gene mutations that may be found:

• Hormone receptor positive (and HER2 negative) cancers: Women with hormone (oestrogen or progesterone) receptor positive cancers are sometimes first treated with hormone therapy (Tamoxifen or an aromatase inhibitor). This may be combined with a targeted drug such as a CDK4/6 inhibitor, Everolimus or a PI3K inhibitor. Women who have not yet reached menopause are usually treated with Tamoxifen or other medicines in combination with medicines that prevent the ovaries from producing hormones. If the disease progresses during hormone therapy, sometimes it is helpful to switch to another type of hormone therapy. For example, if you have been given Letrozole (Femara®) or Anastrozole (Arimidex®), one option may be to use Exemestane, possibly in combination with Everolimus (Afinitor®). Another option would be to use Elasestrant (Orserdu®), Fulvestrant (Faslodex®) or a different aromatase inhibitor, occasionally in combination with a CDK inhibitor (if there is a PIK3CA mutation) (e.g. Alpelisib + Fulvestrant). Approximately one third of metastatic ER positive breast cancers have a PIK3CA gene mutation. Alpelisib (together with the hormone drug Fulvestrant) is a targeted medicine known as a PIK3 inhibitor that can be used to treat postmenopausal women with advanced stage hormone receptor-positive breast cancer. For this medicine to work, a PIK3CA mutation must be found in a biopsy of tumor tissue or cancer cells in the blood. If the cancer no longer responds to any hormone drug, chemotherapy, immunotherapy or PARP inhibitors (such as Olaparib or Talazoparib) may be options, depending on the specific characteristics of the cancer or any gene alterations that may be present.
• Hormone receptor negative cancers: Chemotherapy is the main treatment for women with hormone receptor-negative cancers because hormone therapy is not beneficial for these cancers. If the cancer no longer responds to one chemotherapy regimen, it may be useful to try another chemotherapy regimen. Many different drugs and combinations can be used to treat breast cancer. However, each time the cancer progresses during treatment, the likelihood that further treatment will be effective decreases. Other options include adding an immunotherapy drug to chemotherapy or using a PARP inhibitor alone, depending on the particular characteristics of the cancer or any gene changes that may be present.
• HER2-positive/low cancers: The first treatment given is usually chemotherapy in combination with Trastuzumab (Herceptin®) ± Pertuzumab (Perjeta®), drugs that target HER2. If the cancer progresses, other options may include:

o    An antibody-drug conjugate: for example, Fam-trastuzumab deruxtecan (Enhertu®) or Ado-trastuzumab emtansine (Kadcyla®)

o    A kinase inhibitor [Lapatinib (Tykerb®), Neratinib (Nerlynx®) or Tucatinib (Tukysa®)] in combination with an anti-HER2 drug or chemo drug (e.g. the oral chemo drug Capecitabine) or both. These are used especially for brain metastases.

o    Other drugs targeting HER2 in combination with chemotherapy. E.g. Margetuximab (Margenza®)

o    Hormone therapy may be added to these drug combinations if the cancer is also hormone receptor positive. E.g. a combination of Lapatinib (Tykerb®) and an aromatase inhibitor (for hormone receptor positive cancers).

• Triple negative breast cancer (TNBC): Pembrolizumab, an immunotherapy drug, may be used in combination with chemotherapy in people with advanced TNBC whose tumor makes the PD-L1 protein. The PD-L1 protein is found in about 1 in 5 women with triple negative breast cancer. Immunotherapy with the drug Pembrolizumab may also be used for breast cancers in which the cancer cells show high levels of gene changes called microsatellite instability (MSI) or changes in any of the mismatch repair (MMR) genes (MLH1, MSH2, MSH6 or PMS2). For women with TNBC who have a BRCA mutation, so-called PARP inhibitors (such as Olaparib or Talazoparib) may be considered. For TNBC without a specific gene or protein alteration, chemo alone or the antibody-drug conjugate Sacituzumab govitecan (Trodelvy®) may be an option.

Local or regional treatments

Although the main treatment for stage IV breast cancer is systemic drugs, local and regional treatments such as surgery, radiation therapy or regional chemotherapy are sometimes used. These can help treat breast cancer in a specific part of the body, but are unlikely to cure the cancer completely. These treatments are more likely to be used to help prevent, relieve or eliminate symptoms or complications of the cancer.

Radiation therapy and/or surgery may also be used in certain situations, such as

• To remove a breast tumor when it causes an open or painful sore in the breast (or chest).
• To treat a small number of metastases in a specific area, such as the brain.
• To help prevent or treat metastasis-related bone fractures.
• To relieve the pressure of the cancer on the spinal cord.
• To treat liver blood vessel blockage caused by cancer.
• To provide relief of pain or other symptoms in any part of the body.

Supportive therapy (relief of symptoms of advanced cancer)

Treatment to relieve symptoms depends on where the cancer has spread. For example, pain from bone metastases can be treated with radiation therapy, oral bisphosphonates, parenteral bisphosphonates such as Zoledronic acid (Zometa®) and Pamidronate (Aredia®) or Denosumab (Prolia®).

Treating Recurrent Breast Cancer

In some women, breast cancer can come back after treatment (sometimes years later). This is called a recurrence. Recurrence can be local (in the same breast or in the scar from surgery), regional (in nearby lymph nodes) or distant. Cancer that occurs in the opposite breast without cancer elsewhere in the body is not a recurrent cancer; it is a new cancer that requires its own treatment.

Treatment of local recurrences

In women with local recurrence of breast cancer, treatment depends on the initial treatment.

• If you have had breast-conserving surgery (lumpectomy), local recurrence in the breast is usually treated with mastectomy.
• If mastectomy was the first treatment, recurrence near the mastectomy site is treated by removal of the tumor as far as possible. This is usually followed by radiation therapy if it has not been given before.

In both cases, hormone therapy, targeted therapy (such as Trastuzumab), immunotherapy, chemotherapy or some combination of these may be used after surgery and/or radiation treatment. These medicines may also be used when surgery or radiation is not an option.

Treatment of regional recurrences

When breast cancer recurs in nearby lymph nodes (such as under the arm or around the collarbone), it is treated by removing these lymph nodes if possible. Followed by radiotherapy, if this has not already been given. Systemic treatment (such as chemotherapy, targeted therapy or hormone therapy) may also be considered after surgery.

Treatment of distant relapses

In general, women with recurrence of breast cancer in other parts of the body, such as the bones, lungs or brain, are treated in the same way as women with stage IV breast cancer. The only difference is that the treatment may or may not include treatments or medicines the patient is already taking.

Treatment Success & Prognosis (outlook)

In invasive breast cancers, the 5-year relative survival rates by stage are as follows:

• Localized disease (all Stage I cancers and some Stage II cancers) (cancer has not spread outside the breast): 99%
• Regional disease (some Stage II cancers and all Stage III cancers) (cancer has spread outside the breast to nearby structures or lymph nodes): 85% (90% for Stage II, 70% for Stage III)
• Distant disease (Stage IV cancers) (cancer has spread to distant parts of the body such as the lungs, liver or bones): 30%
• Combination of all phases: 90%,

Survival rates for women with triple negative breast cancer (TNBC) and inflammatory breast cancer (IBC) differ from the above. Non-invasive breast cancer (DCIS) is also considered separately (the 5-year survival rate for DCIS is 100%).

Survival rates are generally grouped according to stage as mentioned above; however, other factors such as patient age, comorbidities and general health status, how well the cancer responds to treatment, tumor grade, presence of hormone receptors in cancer cells, HER2 status, Ki-67 proliferation index, histological/molecular subtype, multigene panels and genomic profiling results, and tumor microenvironment findings (e.g. immune cell infiltration, PD-L1 positivity) also affect treatment success and prognosis; immune cell infiltration, PD-L1 positivity) also affect treatment success and prognosis.

In conclusion, predicting the prognosis of breast cancer is a multifaceted process involving the evaluation of numerous factors. The integration of clinical, pathological and molecular information allows for a more precise understanding of the disease and the adaptation of treatment strategies. As research continues to unravel the complexity of breast cancer biology, new prognostic factors are identified and new targeted therapies are developed, our ability to predict outcomes and improve patient care will further improve.

You can visit our current website "oncosurgery.com.tr" for further information about breast cancer and its surgery.