Lung Cancer Molecular Testing – Who Should Be Tested For Epidermal Growth Factor Receptor Mutations?

Posted by Samantha Powell on June 20th, 2013 |

By Lynne Eldridge MD, About.com Guide / June 20, 2013

One of the greatest advances in lung cancer treatment in recent years has been the use of medications that target epidermal growth factor mutations (EGFR mutations.) For people who test positive for this mutation, medications such as Tarceva (erlotinib) can extend survival and improve quality of life – all without the degree of side effects seen with other forms of chemotherapy.

Yet having the ability to test for this abnormality in cancer ce

Given these numbers, and current thought, 50% of the 80%, or roughly 40% of people with lung cancer – those with lung adenocarcinoma — should be tested. But unfortunately, lung cancer types and subtypes are not always black and white as noted above. For those of you living with lung cancer, many of you are all too familiar with the gray zones.

What do I mean by gray areas? These include tumors that your doctor may describe as having a pathology report that says “mixed phenotype” or “tumor heterogeneity” for starters – words that in plain English mean that a particular tumor can have characteristics that belong to more than one type of cancer. For example, on a lung biopsy sample of lung cancer there may be some parts that look like non-small cell lung cancer and some parts that look more like small cell lung cancer. Some parts of a non-small cell lung cancer may look (and have genetic findings) like adenocarcinoma and some parts may look like squamous cell carcinoma.

A new case report brings to light how this might affect someone with lung cancer. Ordinarily squamous cell carcinomas of the lungs do not have EGFR mutations and do not respond to EGFR inhibitors such as Tarceva. Hence, people with squamous cell carcinoma are not usually tested for EGFR mutations. Yet researchers presented the “case” (as a physician I cringe at that term because behind every “case” is a precious human being) of a 64 year old man with squamous cell carcinoma who did have a tumor that tested positive for an EGFR mutation, and moreover had a prolonged clinical benefit (meaning longer healthy survival) from being treated with a medication that addressed this mutation. Does this mean that squamous cell carcinomas also have EGFR mutations? Possibly, but a much better explanation is that this patient had more than one – what pathologists refer to as mixed – type of tumor. It’s not the exception, but rather a common finding that people with cancer have more than one “variety” of cancer cells.

This is a report of one patient, but the reason I am sharing it with all of you is that it brings up a few very important points for people with lung cancer.

lls, and treating accordingly when it is present, opens a Pandora’s box of sorts. “Who should be treated?”

That one’s not too hard at first glance. The answer is someone who is positive for the mutation. (I mention at first glance because some people have responded to the medication without the mutation, and vice versa.)

But an even bigger question is, “Who should be tested?”

We are learning that EGFR mutations (and subsequent responses to Tarceva) are most common among people who have lung adenocarcinoma – a subtype of non-small cell lung cancers.

So this doesn’t get too confusing, I’ll quickly review the types of lung cancers. The 2 major categories are non-small cell lung cancers which account for about 80% of lung cancers, and small cell lung cancers which make up the remaining 20% or less. Non-small cell lung cancers are further broken down into 3 primary types. These are lung adenocarcinomas (50% of non-small cell lung cancers), squamous cell carcinoma of the lungs (30%) and large cell lung cancers (10%.) Yes, I know these numbers don’t add up to 100, part of the reason being that some tumors have characteristics of more than one type or subtype of lung cancer.

Given these numbers, and current thought, 50% of the 80%, or roughly 40% of people with lung cancer – those with lung adenocarcinoma — should be tested. But unfortunately, lung cancer types and subtypes are not always black and white as noted above. For those of you living with lung cancer, many of you are all too familiar with the gray zones.

What do I mean by gray areas? These include tumors that your doctor may describe as having a pathology report that says “mixed phenotype” or “tumor heterogeneity” for starters – words that in plain English mean that a particular tumor can have characteristics that belong to more than one type of cancer. For example, on a lung biopsy sample of lung cancer there may be some parts that look like non-small cell lung cancer and some parts that look more like small cell lung cancer. Some parts of a non-small cell lung cancer may look (and have genetic findings) like adenocarcinoma and some parts may look like squamous cell carcinoma.

A new case report brings to light how this might affect someone with lung cancer. Ordinarily squamous cell carcinomas of the lungs do not have EGFR mutations and do not respond to EGFR inhibitors such as Tarceva. Hence, people with squamous cell carcinoma are not usually tested for EGFR mutations. Yet researchers presented the “case” (as a physician I cringe at that term because behind every “case” is a precious human being) of a 64 year old man with squamous cell carcinoma who did have a tumor that tested positive for an EGFR mutation, and moreover had a prolonged clinical benefit (meaning longer healthy survival) from being treated with a medication that addressed this mutation. Does this mean that squamous cell carcinomas also have EGFR mutations? Possibly, but a much better explanation is that this patient had more than one – what pathologists refer to as mixed – type of tumor. It’s not the exception, but rather a common finding that people with cancer have more than one “variety” of cancer cells.

This is a report of one patient, but the reason I am sharing it with all of you is that it brings up a few very important points for people with lung cancer.

One is that cancer varies tremendously from person to person. If there were 41 people with lung cancer sitting in a room, there would be 41 different types of lung cancer.

Another point is that it’s important to understand the weakness of current tests we have for accurately diagnosing lung cancer. In the report mentioned above, it was suggested that the nests of tumor cells that were positive for an epidermal growth factor mutation were missed on the patient’s first bronchoscopy. It was only on another bronchoscopy sample that the “other” type of tumor was found.

The take-homes?

If you are having a bronchoscopy, make sure the pulmonologist (lung specialist) who is doing the procedure is experienced, and will attempt to get tissue samples from different areas of the tumor.

According to the authors, people with non-small cell lung cancer that appears to be squamous cell carcinoma who have a remote history of smoking – meaning that they quit some time ago – should also have EGFR mutation testing so that those who are positive can receive highly effective therapy.

Lung cancer is not always one type, but can be a combination of different types. In addition, lung cancers can change over time (develop new mutations.)

Be your own advocate. Ask about molecular testing. If this was not done, ask why. If you aren’t satisfied with the answer, get a second opinion. The management of lung cancer varies considerably in the United States and abroad.

Sources:

Lazarus, D., and D. Ost. How and when to use genetic markers for nonsmall cell lung cancer. Current Opinions in Pulmonary Medicine. 2013. 19(4):331-9.

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