Metastasis – Making the fight against cancer tougher


Cancer in itself is a traumatizing phase in anyone’s life. However, it is more painful when the cancer recurs after the treatment. Cancer recurrence happens due to many reasons. Metastasis is one of those.

About Metastatic Breast Cancer

Sometimes, the cancer spreads to the other parts of the body which are far from the spot where it originated. When breast cancer metastasizes, it is also classified as Stage 4 breast cancer.  It usually spreads to the the lungs, liver, bones or brain. Metastasis is the name of the process by which cancer spreads to the other parts. The chances of metastasis are most amongst breast cancer. The risk of metastatic cancer varies from person to person. Even though cancer spreads to other parts of the body, it is still treated as the original cancer. i.e. breast cancer spread to the lungs will still be considered and treated as breast cancer, not lung cancer.

 How does cancer metastasize?

Cancer usually metastasizes or spreads through one or more of the steps mentioned below-

  • Cancer cells invade healthy cells around them.

When the healthy cell is taken over by the cancer cells, it can replicate more abnormal cells and spread the cancer.

  • Cancer cells penetrate into the circulatory system.

Cancer cells travel through the walls of nearby lymph vessels or blood vessels. Sometimes, they get carried by the lymph system and the bloodstream to other parts of the body and it causes harm.

  • Cancer cells get stuck in capillaries.

Sometimes, cancer cells stop moving as they are lodged in capillaries at a distant location. There, they get divided then migrate into the surrounding tissue.

  • Micro metastases.

Micro metastases are the small tumors formed by cancer cells at the new location. This might make cancer cells spread.

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Image credits – http://cache1.bioon.com/

Symptoms of Metastatic Breast Cancer

The symptoms of metastatic breast cancer vary depending on how far the breast cancer has spread and what type of tissue the new cancer growth has invaded. These symptoms may also vary depending on where the cancer has spread to.

Here are some common symptoms of breast cancer metastasis according to the various locations in the body.

Metastasis to the bone:

  • Bones that are more easily fractured or broken
  • Severe, progressive pain
  • Swelling

Metastasis to the brain:

  • Persistent, progressively worsening headache or pressure to the head
  • Vision disturbances
  • Seizures
  • Vomiting or nausea
  • Behavioral or personality changes

Metastasis to the liver:

  • Jaundice
  • Itchy skin or rash
  • Abnormally high enzymes in the liver
  • Abdominal pain, appetite loss, nausea, and vomiting

Metastasis to the lungs:

  • Chronic cough or inability to get a full breath
  • Abnormal chest X-ray
  • Chest pain

Apart from the above, other nonspecific systemic symptoms of metastatic breast cancer include fatigue, weight loss, and poor appetite.

If these symptoms are noticed in the breast cancer patient, be sure you talk with your physician.

Treatment of metastatic breast cancer is guided by many factors like characteristics of the cancer cells, location where the cancer has spread, its symptoms, and treatments used in past. This treatment is highly personalized and depends on the characteristics of cancer and tolerance of the patient. Side effects are also taken into consideration.

Today, many advanced treatments are available for metastatic breast cancer. Even though the treatments might not guarantee to cure the cancer completely, they definitely help to control it.

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Pharmacogenetics – Selecting Right Drugs For the Right Genes


Did you know that 87%of the total patients receiving cancer chemotherapy develop Adverse Drug Reactions (ADR)? It also causes 50 deaths out of 1000 patients in India. These statistics highlight the importance of correct drugs for the treatment.

Depending on your genetic makeup, some drugs may work more or less effectively for you than they do in other people. Likewise, some drugs may produce more or fewer side effects in you than in someone else.

Pharmacogenetics is the study of inherited genetic differences in drug metabolism which can affect individual responses to drugs, both in terms of therapeutic effect as well as adverse effects. It plays an important role in Oncology.

Now, doctors are able to use information about your genetic makeup to choose the drugs and drug doses that are helpful to you.

For example, if a patient asks for extra amount of codeine to relieve the pain, it can come across as a sign of an evading patient seeking narcotics. However, that patient can be breaking down the codeine within minutes of swallowing it and therefore not be able to create the intermediate molecule that relieves the pain. With this conclusion, the physician can suggest the suitable drugs.

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image credits- static1.squarespace.com/

Pharmacogenomics also help to save you time and money as the “best-fit” drug for you can be chosen from the beginning of the treatment to avoid the trial-and-error approach of giving you various drugs.

Besides pharmacogenomics, other factors may influence how a person reacts to a drug. These include:

  • Person’s age and gender.
  • How advanced the cancer is.
  • Person’s lifestyle habits, such as smoking and drinking alcohol.
  • Other diseases that they have and the medications they are on for these conditions.

FDA Guidelines for Pharmacogenetics

The U.S. Food and Drug Administration (FDA) has listed many drugs that need genetic testing before introducing them in the treatment. Some of them are Mercaptopurine and Irinotecan. FDA recommends genetic testing before giving the chemotherapy drug mercaptopurine (Purinethol) to patients with acute lymphoblastic leukemia. It also advises doctors to test colon cancer patients for certain genetic variants before administering irinotecan (Camptosar), which is part of a combination chemotherapy regimen.

Let us see some case studies so that we can understand how pharmacogenetic analysis helped patients with better drugs, and thus, treatment.

  1. A 62 year old male patient with colon cancer was started with a standard dose of FOLFOX and after 6 weeks, Irinotecan and Cetuximab were introduced. However, after the first cycle, sever Myelo-suppression was developed. It delayed the chemo for 3-15 days every cycle. At DGL, comprehensive pharmacogenetic analysis consisting of tumour mutation analysis was advised which confirmed ADR to Irinotekan and 5FU and capsitaben was recommended.
  1. 52 year old male Chronic Smoker diagnosed with adenocarcinoma of the Right Lung with liver metastasis was given Pemetrexed and Carboplatin- 6 cycles which showed partial response. He was advised comprehensive pharmacogenetic analysis at DGL consisting of Tumor mutation analysis for efficacy evaluation and Pharmacogenetics for toxicity profile that showed KRAS mutation which explains partial response to Pemetrexed. Other mutations detected suggestive of personalized targeted therapy.

Geneshield Test at DGL

This test at DGL requires sample of whole blood/ saliva and turnaround time is 2 weeks. The report will give you the information of the genetic mutations you carry that would affect the efficacy of drugs. This test also gives you information about the toxicity of these drugs on your body at the same time.

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It’s always better to maintain a good rapport with the doctor. Here are the few things which you should discuss with your doctor before starting a treatment.

  • Would you explain my treatment options?
  • Which treatment or combination of treatments do you recommend? Why?
  • What are the possible side effects of this treatment?
  • Is there a way to predict how the cancer will respond to this drug or whether I might experience severe side effects?
  • What are my options if the cancer does not respond to the drug or if I suffer from severe side effects?

Detecting the ill-effects of drugs and replacing them with proper ones under expert advice definitely help to give the treatment a right direction.

 

 

 

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Role Of Genetics In Breast Cancer and BRCA-1 & 2 Mutations


“I know my children would never have to say- mom died of cancer!” said Angelina Jolie- famous Hollywood actress after her decision of preventive surgery for ovarian cancer where she had her ovaries and fallopian tubes removed. BRCA mutation was found in her tests and three women in her family; including her mother had died of cancer. Thus, she had to take a preventive measure.

Genes and genetic variations in our body contribute to the bodily functions and overall health. This also includes the possibility of having various diseases which are hereditary or developed in our body due to changes in the genetic codes.

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Each cell in our body consists of genes that have genetic code for our body. These codes contain the information regarding various functions of our body for example – when the cells grow, divide, and die. Changes in these genetic codes are called mutations. Many of these are harmless; while some increase the risk of diseases like breast cancer. BRCA are inherited mutations; thus you need to undergo this test only once. I.e. they do not develop during our lifetime.

According to the American Journal of Human Genetics and Journal of Clinical Oncology, around 55-65% of women with confirmed BRCA mutation will develop breast cancer by the age of 70 and their immediate family members have 50% chances of possessing the same risk.
It’s not only women who are at risk; while women have 85% risk of breast cancer and 40% risk of ovarian cancer; men too have about 20% risk of prostate cancer and/ or male breast cancer.

Thus, to examine the risk of it, Datar Genetics Limited has introduced a test using NGS platform that has 99.9% analytical sensitivity and 100% specificity and accuracy. NGS means Next Generation Sequencing. It enables us to examine the genetic mutations in members of families with high incidence of cancer.

BRCA -1 & BRCA – 2 are two genes which are linked to HBOC (Hereditary Breast & Ovarian Cancer) these genes produce tumor suppressor proteins which help to repair damaged DNA. When either of these genes have mutations, it increases the risk of cancer.

BRCA 1 & BRCA 2 testing should be considered if:-

  1. You had breast cancer at early age
  2. Your mother, sister, or daughter had breast cancer at early age or ovarian cancer.
  3. You are a woman with 1st degree relative who’s diagnosed with bilateral breast cancer before age of 50
  4. The men in your family have strong history of breast/ ovarian cancer.

Genetic testing

A doctor/ genetic counselor helps you decide whether genetic testing is appropriate for you. In most cases, test is primarily done on the person in the family who has breast cancer. If mutation is not found, other family members need not be tested.

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image description

The test includes counseling and a blood test and you can get the results in around two weeks.

It is very important for you to know if you are at a risk of mutation and you should ask your doctor what tests and precautions should be taken to lower the risk.

Women who have BRCA 1 gene mutation are at higher risk of triple negative breast cancer while BRCA 2 carriers have breast cancers that are Estrogen Receptor positive. BRCA 1/2 mutations increase the risk of ovarian cancer. Men with BRCA 2 mutation have increased risk of prostate and breast cancer.

Risk reduction options:-

Following are the recommended cancer screening tests:-
  1. Breast Self Examination/ Clinical Breast Exam (CBE)
  2. Mammography
  3. Breast Magnetic Resonance Imaging

There are also some risk lowering options for BRCA1/2 carriers, like- FDA approved drugs and treatments like prophylactic mastectomy and prophylactic oophorectomy.

Timely examinations and preventive treatments are best way to lower the risk of breast cancer.

 

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