Lab Testing and Breast Cancer

 Breast cancer are a type of malignant tumor that is the result of uncontrolled cell growth within the breast. They mainly occur in the ducts which transport milk over to the nipple during lactation (breastfeeding) and occur in the lobules, which are the milk-producing glands.  

Each type of cancer has its own characteristics. Some are aggressive, while others are slow growing. Some are highly sensitive to progesterone and estrogen hormones, while others produce high levels of specific proteins that promote growth. The characteristics of a certain type of cancer can affect which treatment methods are used as well as the potential that cancer will recur.  

Every year, U.S. women are diagnosed with breast cancer more than any other form of cancer except for skin cancer.  About 1 in 8 women in the U.S. develop invasive breast cancer at some point in their lives. It is estimated by the American Cancer Society that around 270,000 new invasive breast cancer cases will be diagnosed in American women every year and that an estimated 42,000 women die from this disease. Breast cancer can also be developed by men. It is estimated by the American Cancer Society that around 2,7000 men get diagnosed with breast cancer every year, and around 500 men die from it. 

Risk Factors 

It is possible for people to develop breast cancer at any age. However, the risk of developing the disease increases as women grow older. Most cases of breast cancer develop for reasons that are not yet understood.  

The following are examples of some of the factors that may increase the risk to develop breast cancer:  

  • Being obese 
  • Family history – having close relatives (i.e., father, brother, uncles) who have had cancer 
  • Estrogen treatment (e.g., hormone replacement therapy following menopause, some forms of birth control)  
  • Not breastfeeding, having one’s first child after the age of 30, not having children  
  • Cancer in the person’s other breast  
  • Consumption of alcohol (higher consumption amounts increase risk) 
  • Not exercising enough  
  • BRCA1 or BRCA2 Mutations 

BRCA1 and BRCA2 are inherited mutations within breast cancer genes. Around 5-10% of breast cancers are hereditary.  BRCA1/BRCA2 mutation is the most common hereditary breast cancer cause. They are two tumor suppressors genes that produce proteins to suppress the abnormal growth of cells to help prevent cancer. Mutations in those genes may affect their normal functioning, which allows for the uncontrolled growth of cells, which increases the risk of developing cancer.  Women who have inherited BRCA2 or BRCA1 mutations, respectively have around a 72% or 69% lifetime risk to develop breast cancer.  

For women who have a BRCA2 or BRCA1 gene mutation (referred to as a pathogenic variant at times) that increase breast cancer risk, one option is a prophylactic mastectomy.  Women who choose this election have both of their breasts removed before they develop cancer instead of running a high risk to develop the disease later. It has been shown in studies that surgery may lower the risk by up to 95% of developing cancer.  Other women choose to have a   prophylactic mastectomy done on their breast that is cancer-free after their other breast has developed cancer. A health practitioner can help to work with and advise a woman who is thinking about having a prophylactic mastectomy. 

Leading a healthy lifestyle, including avoiding alcohol, maintaining a healthy level of body weight, and regular exercise can help to reduce the risk of a person developing breast cancer. There continue to be more factors identified by research studies that are associated with a decreased or increased risk of developing breast cancer. However, there is no one set of actions that will prevent or cause breast cancer.  Women should consult with their healthcare providers to determine what their risk factors are and the best way to address them. As an example, a woman might decide to avoid using hormone replacement therapy long term. 

Women who have a high risk of developing breast cancer might be able to lower their risk by taking medications. However, there are significant side effects associated with these drugs, including increased risk for developing cardiovascular disease, endometrial (uterine) cancer, and blood clots. Deciding to take medication must be weighed carefully. You should consult with your healthcare practitioner to help assess the benefits and risks of this form of treatment.  

Symptoms and Signs  

It is critical to keep in mind that most of the lumps in a breast are benign and not cancerous, and signs and symptoms that are associated with breast cancer might be due to some other cause. Some of the potential symptoms and signs include the following:  

  • Lump or bass in the breast  
  • Changes in appearance, shape, or size of the breast 
  • Flaking, scaling, peeling or pigmented skin in the area surrounding the nipple 
  • Lumps or swelling in the underarm lymph node  
  • Nipple discharge and/or pain 
  • Breast pain or swelling 
  • Nipple retraction 
  • Breast skin thickening, reddening, or dimpling 

Inflammatory breast cancer (IBC) is a rare type of breast cancer and might not form as a lump. Some of this condition’s symptoms may be similar to a breast infection, which includes ridged thickened skin, itching, breast swelling, tenderness, and warmth of the breast.  

Screening and Early Detection  

Breast cancer survival is strongly influenced by the early detection of breast cancer. For example, whenever breast cancer is detected in the localized, early-stage, 99% of these patients survive for five years, at least after being diagnosed.  

Breast Self-Awareness and Clinical Breast Exam  

According to the National Comprehensive Cancer Network (NCCN) and American College of Obstetricians and Gynecologists (ACOG) state that women should be provided with a clinical breast exam every 1 to 3 years by a healthcare professional for women 25 to 39 years old as part of their regular overall health exam and once per year for women who are 40 years old and older.  

According to the NCCN and ACOG, breast self-awareness is very important. Breast self-awareness should be discussed by women of all ages with their healthcare providers and report any changes to the normal feel and appearance of their breasts immediately. Those changes may include redness, discharges other than breast milk, a mass, and pain.  


Along with clinical breast exams, a mammogram is the other major early detection tool. It is widely recognized within the medical community that mammography and breast cancer screening is very valuable. However, there are differences in the advice that is given when it comes to how frequently they should be conducted or when they should start. Most health organizations agree that women and their healthcare providers should work together to assess what their risk is for developing breast cancer as well as determine the best course of action. They should discuss the harms as well as benefits of screening. Although screening can detect cancer early on when it is the most treatable, it can also produce false-positive results, which can cause unnecessary follow-up procedures like biopsies and anxiety.  

Laboratory Testing  

Breast cancer testing’s main goals are to:  

  • Diagnose and detect breast cancer during its earliest stages 
  • Properly identify genetic risk within high-risk women 
  • Determine how far breast cancer has spread  
  • Evaluate the characteristics of cancer to guide treatment  
  • Monitor over time how effective the treatment is and the individual to detect as well as address any recurrences of cancer  

Some of these tests, the samples that are required might involve using a syringe and thin needle to aspirate cells from the breast (FNA or fine-needle aspiration) or using a bigger bore needle (for a core needle biopsy) to remove a solid piece of tissue, or by surgically removing a tumor or breast tissue (an open biopsy).  

Mammogram – Highly-sensitive X-ray digital technology might detect small lumps that a clinical breast exam would not detect. 

BRCA1 / BRCA2 (Blood) – If there are genetic mutations present it can suggest around a 70% lifetime risk.    

HER2 (Tissue) – A test for amplification of the gene coding for a protein or for the overexpression of HER2 proteins. Tumors that are positive might respond well to or another medication targeting HER2. 

Progesterone (Tissue) – Increased levels suggest hormonal therapy Estrogen Receptor is responding well.                              

CA 15-3/ CA 27.29 (Blood) – A specific cancer antigen is measured by these tests. Elevated Blood levels might indicate cancer has recurred following initial treatment.  

Breast Cancer Gene (Tissue) – Genetic tests used for predicting prognosis. 

Expression Tests – by estimating the risk of spread (metastasis) and recurrence of cancer and to guide treatment.  

Genetic risk: 

BRCA2 or BRCA1 gene mutation – Women at high risk due to a strong family or personal history of ovarian cancer or early-onset breast cancer can learn whether they have a BRCA gene mutation. If either gene has a mutation, it is an indication that the individual has a much higher lifetime risk (69% to 72%) to develop the disease.  However, it is very important to keep in mind that only around 5-10% of all breast cancer cases take place in women who have a BRCA gene mutation. People should consider genetic counseling both before testing and after positive test results are received.  

Mutations that occur in other genes also can increase the risk of inherited breast cancer. However, they are not as common as BRCA mutations are, and these mutations increase the risk a lot less compared to BRCA mutations. Some of these other gene mutations include PALB2, STK11, PTEN, CHEK2, and ATM. Some labs provide panels of tests that can detect mutations in one or several of those genes. 

Diagnosis: Surgical Pathology and Cytology  

When a suspicious area is detected by a radiologist, such as a non-palpable mass from a mammogram, hardened tissue (calcifications), or a lump that was discovered in a clinical breast exam (like Non-Laboratory Tests discussed below), then one of the following tests will often be ordered by a healthcare practitioner:  

Fine needle aspiration (FNA) – a syringe and a thin needle is used to remove a cell sample from the part of the breast that is suspicious  

Core needle biopsy – a bigger bore needle is used for removing a solid piece of breast tissue; one or several core samples might be removed.  

Surgical biopsy – a doctor cuts out part of the lump in the breast. 

A pathologist in each case microscopically examines the cells in the breast for any signs of cancer. The pathological exam is performed to determine whether the lesion is malignant or benign.  

Cells that are malignant show deviations or changes from normal cells. Some of the major signs include changes in the appearance, shape, and size of the cell nuclei along with increased cell division evidence. Malignant cells may also distort the normal cell arrangements inside the breast tissue. Based on these observed changes, pathologists can diagnose cancer, determine how abnormal cells seem, and determine whether it is a mixture of changes or one kind of change. Those results can help to guide the most appropriate breast cancer treatment that should be used. 

Due to sample size, core needle biopsy, and needle aspiration are limited. A tissue biopsy is frequently needed to determine if cancer is invasive or in its early stages. When breast cancer is removed surgically, cells from the tumor and, at times, the adjacent lymph nodes and tissues are examined by a pathologist to help determine how much cancer has spread. 

Determine the appropriate treatment options: 

If breast cancer is diagnosed by the pathologist, several tests can be conducted on the tissue cancer cells. The test results offer a prognosis to help the cancer specialist (oncologist) guide the best treatment for the patient. HER2, as well as progesterone and estrogen receptors, are the most useful.  

HER2 is a type of oncogene that is associated with the growth of cells. There are two HER2 gene copies in normal epithelial cells, and low HER2 protein levels are produced on the cell surface. In around 20% to 30% of invasive cell cancers, protein is over-expressed, and the HER2 gene is also amplified. The tumors are susceptible to targeted treatment that binds specifically to the overexpressed protein. Women who have amplified HER2 genes tend to respond well to those drugs, and their prognosis is good.  

Progesterone and estrogen (PR and ER) status are critical for predicting the disease’s course and to help to guide the treatment process. Breast cancer cells with progesterone and/or estrogen receptors may bind progesterone and estrogen. The female hormones help to promote the growth of cells in PR and ER-positive cancers. The higher the percentage of positive cancer cells, in addition to the higher intensity (number of receptors in each cell), the better the person’s prognosis will be. That is because hormone-dependent cancer responds well quite often to hormonal therapy that lowers estrogen levels or blocks estrogen.  

Breast cells that are HER2 amplification negative and negative for both progesterone and estrogen receptors are referred to as “triple-negative.” This form of breast cancer takes place more frequently in your women as well as women of Hispanic or African descent. Women who have BRCA mutations might be predisposed to having triple-negative breast cancer. 

Triple-negative breast cancers tend to spread and grow faster than other types, and the prognosis is also worse. Since the cells do not possess HER2, they do not respond positively to targeted treatment. They also do not have receptors for progesterone and estrogen and may not be treated with therapy to block the hormones. However, other forms of chemotherapy can be used to treat them. Currently, new studies are underway for evaluating new drugs and to determine if treatment with the drugs by themselves or in combination with chemotherapy can be used for triple-negative breast cancer treatment.  

Monitoring treatment: 

Cancer antigen 15-3 (CA 15-3) is a protein that normal breast cells produce. In many women who have breast cancer, there is increased production of both CA 15-3 as well as a related cancer antigen 27-29 (CA 27-29). Cancer is not caused by CA 15-3. Instead, tumor cells shed the protein, and it enters the blood, which makes it a useful tumor marker for following cancer’s course. There is elevated CA 15-3 in only around 10% of women who have early localized breast cancer. However, it is elevated in around 80% of women who have metastatic breast cancer. There can be blood test orders for CA 27.29 or CA 15-3 at intervals following treatment to help monitor for potential breast cancer recurrence in a woman. These tests are not used for screening for breast cancer but may be used to monitor in some women after they are diagnosed.  

Other tests: 

Several other tests are also available, while many others are being researched currently to evaluate many different genetic patterns that occur in the tissue of breast cancer tumors. The breast cancer gene expression tests are new, but they are becoming used more often.  They can be used in the form of predictive tests for breast cancer recurrence as well as therapy outcomes. Oncotype DX Breast and MammaPrint are two of these tests that are most ordered.  

Additional tests can be used for certain breast cancer cases, like Ki-67, DNA ploidy, or other markers. These tests are used by some medical centers for additional information when evaluating women who have breast cancer. However, most authorities believe that the most important ones to evaluate first are progesterone and estrogen receptor status as well as HER2.