Breast Cancer

Breast cancer can be invasive or non-invasive (cancer in situ). Invasive breast cancer is cancer that has spread to surrounding tissues. Non-invasive breast cancer does not spread to surrounding tissues. Most breast cancers start in the milk ducts or lobules of the breast and are called ductal carcinoma or lobular carcinoma, respectively.

Ductal carcinoma of the breast .
These cancers begin in the cells that line the milk ducts and make up the majority of breast cancers.

Ductal carcinoma in situ (DCIS) of the breast .
This is cancer that is only in the breast duct and has not spread to surrounding tissues.

Invasive ductal carcinoma of the breast.
This is cancer that has spread outside the duct, infiltrating the surrounding breast tissue.

Lobular carcinoma of the breast (lobular breast carcinoma).
This is cancer that begins in the lobules.

Lobular carcinoma in situ (LCIS).
LCIS is found only in the lobules. LCIS is not an invasive cancer. However, LCIS is a risk factor for developing invasive breast cancer in both breasts.

Invasive lobular breast carcinoma.
This is cancer that has spread outside the lobules, meaning it has invaded the surrounding breast tissue.

Less common types of breast cancer include:

• Medullary carcinoma of the breast
• Mucinous carcinoma of the breast
• Tubular carcinoma of the breast
• Metaplastic breast carcinoma
• Papillary breast carcinoma
• Inflammatory breast carcinoma (is a faster-growing type of cancer that accounts for about 1% to 5% of all breast cancers).
• Paget’s disease is a type of cancer that starts in the ducts of the nipple of the breast. Although it is usually non-invasive, it can also be an invasive cancer.

There are 3 specific subtypes of breast cancer that are determined by specific tests (Immunohistochemistry, IHC) on a tumor sample. These tests will help your doctor learn more about your cancer and decide on the most effective treatment plan.
These tests on the tumor sample can find out if the cancer is:

Hormone-dependent cancer (positive in hormonal markers).
Breast cancers that express estrogen receptors (ER) and/or progesterone receptors (PR) are called hormone receptor-positive. These receptors are proteins found on cells. Tumors that have estrogen receptors are called “ER-positive.” Tumors that have progesterone receptors are called “PR-positive.” Only one of these receptors needs to be positive for the cancer to be called hormone receptor-positive. Hormone receptor-positive cancer depends on the hormones estrogen and/or progesterone to grow.
Cancers that are hormone receptor-positive can occur at any age, but are most common in women who have gone through menopause. About 60% to 75% of breast cancers are estrogen and/or progesterone receptor-positive. Cancers that are not hormone receptor-positive are called “hormone receptor-negative cancer.”

HER2-positive breast cancer.
About 15% to 20% of breast cancers depend on a gene called human epidermal growth factor receptor 2 (HER2) to grow. These cancers are called “HER2-positive” and have many copies of the HER2 gene or high levels of the HER2 protein. The HER2 gene makes the HER2 protein, which is found on cancer cells and is important for cancer cell growth.

HER2-positive breast cancers grow more quickly. They can also be hormone receptor positive or hormone receptor negative.
Cancers that have no or low levels of the HER2 protein and/or few copies of the HER2 gene are called “HER2-negative” breast cancers.

Triple-negative breast cancer (TNBC).
If a tumor does not express the estrogen receptor ER, the progesterone receptor PR, or the HER2 protein, the tumor is called “triple-negative.” Triple-negative breast cancer accounts for about 15% of invasive breast cancers. Triple-negative breast cancer appears to be more common in younger women, especially younger women of color. Triple-negative cancer is also more common in women with a mutation in the BRCA1 or BRCA2 genes.
Experts recommend that all people with triple-negative breast cancer who are younger than 60 years of age should be tested for BRCA1 & BRCA2 gene mutations.

For most types of cancer, a biopsy is the only sure way for a doctor to know if an area of ​​the body has cancer. In a biopsy, the doctor takes a small sample of tissue for histological examination in a pathology laboratory.
This list describes options for diagnosing this type of cancer. Not all of the tests listed below are used for every person. Your doctor will consider the following factors when choosing a diagnostic test:

• • The type of cancer suspected
  • Your symptoms
  • Your age and general health status
  • The results of previous medical examinations

The series of tests needed to evaluate a possible breast cancer usually begins when your doctor discovers an abnormal change or calcification on a mammogram or if a lump is found in the breast during a clinical exam or self-examination. Less commonly, redness or swelling of the breast or a lump or nodule under the arm, in the armpit, may be observed.

The following tests may be used to diagnose breast cancer or to conduct follow-up after a diagnosis of breast cancer:
1. Mammography
2. Ultrasound
3. Magnetic resonance imaging (MRI)
4.Biopsy.

Biopsy is the removal of a small amount of tissue for histological examination under a microscope. Only a biopsy can make a clear final diagnosis. A pathologist is a doctor who specializes in interpreting histological examination to evaluate cells, tissues and organs for the purpose of a final diagnosis.

There are several types of biopsies, which are classified based on the technique and/or size of the needle used to collect the tissue sample.

Fine needle aspiration biopsy.
This type of biopsy uses a thin needle to remove a small sample of cells.

Needle core biopsy.
This type uses a larger-diameter needle to remove a larger sample of tissue.

Surgical biopsy.
A surgical biopsy removes a larger amount of tissue. Most often, core biopsies are the ones recommended for diagnosing breast cancer. This means that only 1 surgery is needed to remove the tumor and take samples from the lymph nodes in the armpit.

Image-guided biopsy.
During this procedure, a needle is guided to the appropriate location (where the lesion appears to be) with the help of an imaging technique, such as a mammogram, ultrasound, or MRI.

Sentinel lymph node biopsy.
This procedure is a way to see if there is cancer in the lymph nodes near the breast.

Histological examination of the sample removed during the biopsy can help your doctor learn about specific characteristics of the cancer that help determine treatment options.

Tumor characteristics.
Histological examination of the tumor under a microscope is used to determine whether the cancer is invasive, whether it originated in the breast ducts or lobules, and whether the cancer has spread to the lymph nodes (metastasis).
The surgical margins of the tumor are also checked and their distance from the tumor is measured.

Hormones ER (estrogen) and PR (progesterone).
Testing for ER and PR (see Specific Types of Breast Cancer), done with Immunohistochemistry (IHC), helps determine a patient’s risk of recurrence and the type of treatment that is most likely to reduce the risk of recurrence. ER and PR are also often measured in carcinoma in situ (DCIS) (see Types of Breast Cancer).

In general, hormone therapy works well for ER-positive and/or PR-positive cancers.

HER2-positive cancer.
HER2 status (see Specific Types of Breast Cancer) helps determine whether drugs that target the HER2 receptor, such as trastuzumab (Herceptin, Ogivri), can help treat the cancer. ASCO and the College of American Pathologists (CAP) recommend that HER2 testing be done when a patient is first diagnosed with invasive breast cancer.

If the cancer has spread to another part of your body (metastasis) or has come back after treatment (recurrence), you should be tested again on the new tumor that has appeared or in areas where the cancer has spread, especially if the results will affect your treatment options.
Talk to your oncologist about the best combination of tests for you.

If the test results are not clearly positive or negative, you may need to be tested again, either on a different tumor sample or with a different test. Sometimes, even with repeated tests, the results may not be conclusive, so you and your doctor will discuss the best treatment option.
If your cancer is HER2 positive, then an anti-HER2 therapy may be the recommended treatment option for you. If your cancer is HER2 negative, anti-HER2 therapy is not a treatment option for you, and your doctor will give you other options for treating your breast cancer.

Tumor grade.
Tumor grade is also determined in the histological examination after a biopsy and refers to how different the cancer cells look from healthy cells and whether they grow slowly or quickly. If the cancer looks like healthy tissue, it is called “well-differentiated” or “low-grade.” If the cancer tissue looks very different from healthy tissue, it is called “low-grade cancer” or “high-grade.”

There are 3 grading levels: Grade 1 (well-differentiated), Grade 2 (moderately differentiated), and Grade 3 (low-grade).

Molecular testing of the cancer.
Your doctor may recommend other laboratory tests on the tumor sample to identify specific genes, proteins, and other factors unique to the tumor.
If you have locally advanced or metastatic breast cancer, your doctor may recommend testing for the following molecular characteristics:

1) PD-L1 testing, a protein found on the surface of cancer cells and certain immune system cells. This protein prevents the body’s immune cells from destroying the cancer.

2) Test for microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR).
Tumors that have MSI-H or dMMR have difficulty repairing damage to their DNA. This means they develop many changes or mutations. These mutations make certain proteins in the cancer cells abnormal, which makes it easier for immune cells to find them and attack the tumor.

3) NTRK gene fusions.
This is a specific genetic change found in a number of cancers, including breast cancer.

There are many other genes, biomarkers and proteins that can be targeted in breast cancer, such as BRCA1, BRCA2, RET, PALB2, PIK3CA, AKT1, ESR1, PTEN. Consult your Oncologist for the best choice and individualization for you.

By analyzing many genes and proteins simultaneously, this test offers a detailed molecular profile of lung cancer, based on which your clinician (oncologist) will select the optimal treatment for you individually.

Mutations in the tumor suppressor genes BRCA1 & BRCA2, ATM, BARD1, BRIP1, CDK12, CHEK2, FANCD2, MRE11, NBN, PALB2, PPP2R2A, RAD51B, RAD54L, TP53 account for a large number of hereditary cancer cases.

HaemArray Breast was developed as a method for identifying genetic mutations associated with hereditary breast, ovarian, prostate and pancreatic cancers.

The aim is prevention and early diagnosis in the initial and more curable stages of the disease. The test can also help in choosing a treatment regimen and inform members of the wider family about the risk of developing cancer.

The tests are performed on the surgical specimen (paraffin cubes) or the biopsy material (paraffin cube) from which your histological examination was performed or on the aspiration material (FNAB, EBUS) from which your cytological examination was performed. In our fully integrated Laboratory, the pathologist selects the most appropriate & representative paraffin cube, ensuring that the most appropriate sample will be used for the tests. Qualitative and quantitative parameters are checked.

In case your sample is not already at Microdiagnostics archive, please contact us immediately so that we can arrange for its safe and rapid transport to our laboratory. You will also need to quickly and easily complete the Consent Form.

Most of the time, the sample material we are called upon to handle is small because it has resulted from a minimally invasive method (needle biopsy, fluid aspiration, paraffin block with minimal material).

In our laboratory, Pathologists check in a timely manner whether the material to be examined is sufficient. If so, then a management algorithm is followed, with the aim of achieving the performance of multiple tests on the material (Immunohistochemistry, real-time PCR, NGS) in order to fully check the molecular profile of your tumor (proteins, genes, histological Grading).

In this case, and once sample enrichment manipulations have been exhausted, we contact your clinician to discuss alternative approaches in order to obtain the desired information to select the optimal treatment for you. Some examples:

• • • Performing an alternative test (e.g. Immunohistochemistry instead of PCR, or choosing Next Generation Sequencing (NGS))
    • Performing Immunohistochemistry instead of FISH (Fluorescent In Situ Hybridization) and vice versa
    • Possible blood sampling instead of tissue testing (liquid biopsy)
    • Possible option to take a new biopsy or puncture

A small amount of blood (~10 ml) is taken, as in a routine hematology test. In the event that the blood collection is not performed at Microdiagnostics facilities by appointment, the blood should be collected in a 10ml EDTA blood vial.

Transport conditions: The blood vial is kept at refrigerator temperature (preservation) and after collection, it is recommended to be transported at Microdiagnostics facilities as soon as possible.

Contact us at 2310 23 22 72 and we will immediately assist you in quickly transporting the sample to our laboratory.

By cash, bank card, bank deposit, or Online interbank deposit.

One of the primary concerns at Microdiagnostics is the protection of your personal data as well as the strict observance of the conditions of protection of your genetic material and medical results. In full compliance with the General Data Protection Regulation (GDPR), we ensure that any test performed is done with your knowledge and consent and we do not communicate results over the phone.