Cancer

Robert Miller MDwww.aboutcancer.com

What is Cancer?

“Cancer is a name given to a collection of related diseases, where some of the body’s cells begin to divide without stopping and spread into surrounding tissue.”

www.cancer.gov

What Causes Cancer?

Cancer is a genetic disease—that is, it is caused by changes to genes that control the way our cells function, especially how they grow and divide.

Genetic changes that cause cancer can be inherited from our parents(germ line). They can also arise during a person’s lifetime as a result of errors that occur as cells divide or because of damage to DNA caused by certain environmental exposures (somatic mutations).

Each person’s cancer has a unique combination of genetic changes. As the cancer continues to grow, additional changes will occur.

‘Driver’ MutationsEach cancer is characterized by numerous somatic mutations, of which only a subset contributes to the tumor’s progression.

Scientists want to be able to distinguish these “driver” mutations from the preponderance of neutral “passenger” mutations that characterize each cancer,

Genetic Drivers of CancerThe genetic changes that contribute to cancer

tend to affect three main types of genes:Proto-oncogenes are involved in normal cell growth and division. When these genes are altered they may become cancer-causing genes (or oncogenes), allowing cells to grow and survive when they should not.

Tumor suppressor genes are also involved in controlling cell growth and division. Cells with certain alterations in tumor suppressor genes may divide in an uncontrolled manner.

DNA repair genes are involved in fixing damaged DNA. Cells with mutations in these genes tend to develop additional mutations in other genes. Together, these mutations may cause the cells to become cancerous.

Understanding CancerType: there are more than 100 types of cancer. The cancer is

usually named after the site where it starts and are called carcinoma. There are unusual types like sarcoma, leukemia, myeloma or lymphoma. The biopsy or pathology report will describe the type of cancer and often include multiple other important factors that can effect the prognosis (or outcome).

Stage: how far the cancer has spread. There are generally 4 stages of each type of cancer and currently the AJCC (American Joint Committee on Cancer) 7th edition staging system is used which came out in 2010. The pathology report, the findings from surgery (if done) and imaging studies (e.g. CT scans, MRI scans, PET scans) are all used to try to determine an accurate stage.

Path Report

The diagnosis of cancer usually starts with a biopsy of the tumor (histology) or cancer mass (if possible) or collection of cells (cytology) from the patient. Important things to look for on a pathology report:

1. Type of cancer (where did it start and is it a specific subtype) 2. Invasive or not3. Size and depth of invasion4. Other structures invaded (like lymph nodes or nearby

structures)5. Grade or measure of how mutated or fast growing the cancer

is6. Margins (has it been completely removed)7. Other specific risk or prognostic factors (hormone receptors,

vascular or perineural invasion, proliferation score, ulceration and many other important site specific factors)

8. Genetic profile (e.g. BRACA, ALK, HER2, luminal, Oncotype DX,

EGFR, etc. including NGS or next generation sequencing)

Genetic Profile

Oncotype will determine the risk of a recurrence

Genetic Profile

MammaPrint will determine whether adding chemotherapy (CT) to endocrine therapy (ET) will improved the cure rate

Genetic Profile

Prosigna will classify breast cancer into a molecular category that will have much different risks of recurrence

Using Adjuvant Online to Calculate the Benefit from taking Chemotherapy based on genetic recurrence risk score

Low risk

High risk

Understanding CancerStage: how far the cancer has spread.

There are generally 4 stages of each type of cancer and currently the AJCC (American Joint Committee on Cancer) 7th edition staging system is used which came out in 2010.

The pathology report, the findings from surgery (if done) and imaging studies (e.g. CT scans, MRI scans, PET scans) are all used to try to determine an accurate stage.

Understanding The Stage

AJCC 7th Ed Staging System is based on the TNM SystemT: stand for tumor and cancer be based on size or depth of invasion and commonly goes from T0 to T4N: stands for lymph node spread based on the number of nodes, size of nodes or location of nodes and is usually from N0 to N3M: stands for evidence of distant metastases and is usually M0 or M1

Stage: generally combines all 3 of these (and sometime other factors as well) to group patients into stage categories generally from 0 to 4 but can include sub stages like IVa , IVb or IVc

For breast cancer, the size and number of nodes combine to determine the stage

For colon cancer, the depth of invasion is critical to determine the stage

Understanding The Stage

Why is the stage important?

Because it guides treatment strategies and predicts outcome and survival.

Survival by Stage for Breast Cancer

Years

0III

III

IV

Understanding Treatment Options

Treatments

1.No treatment (either unnecessary, won’t work anyway, it’s not worth it to the patient)

2.Surgery3.Radiation4.Chemotherapy

1.Conventional chemotherapy2.Hormone Therapy3.Immunotherapy4.Targeted Therapy/ Precision

Medicine

Surgery : local treatment, may be disfiguring but if the tumor can be removed it is quite successful

Radiation: regional treatment, may have less side effects then surgery, successful if the cancer is radio-sensitive

Chemotherapy: widespread, treats the whole body, may have significant side effects, success depends completely on whether the cancer is sensitive to the available drugs

Basic Treatments

Combined Modality Therapy in the Treatment of Pediatric

Rhabdomyosarcoma

Treatment 5 Year Survival

Surgery 10 – 20%

Surgery plus PostOp Radiation 40 – 50%

Surgery, Rad. then Chemotherapy 80 – 90%

Precision TherapyPrecision or targeted therapies work by exploiting the molecular underpinnings of cancer. The precision of cancer treatments has become more sophisticated with each passing year.

Therapies that attack multiple genetic drivers of cancer in combination or harness the body’s own immune system to attack tumor cells have improved outcomes for patients with difficult-to-treat cancers.

Of all the newly FDA-approved cancer therapies approved in 2015, 12 (62.5%) are classified as precision therapies. 

New Cancer Drugs and Biological FDA Approved in 2015

Best Treatment

How do patients know if they are receiving the best, current available therapy?

Treatment decisions should be made by the patient and family in consultation with a multi disciplinary panel of cancer specialists c/w current NCCN guidelines. These can be accessed free online at NCCN.org or the patient site at www.nccn.org/patients

Treatment decisions should be made by the patient and family in consultation with a multi disciplinary panel of cancer specialists c/w current NCCN guidelines

Should be a Team Approach

www.nccn.org/patients

PrognosisNote that there are many factors that effect the odds and length of survival1.The type and location of the cancer2.The stage and site of spread3.The cancer grade or speed of growth4.Other specific traits of the cancer cell5.The patient’s own health,

age and performance score6.The response to treatment

0 – Asymptomatic (Fully active, able to carry on all pre-disease activities without restriction)1 – Symptomatic but completely ambulatory (Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature. For example, light housework, office work)2 – Symptomatic, <50% in bed during the day (Ambulatory and capable of all self care but unable to carry out any work activities. Up and about more than 50% of waking hours)3 – Symptomatic, >50% in bed, but not bedbound (Capable of only limited self-care, confined to bed or chair 50% or more of waking hours)4 – Bedbound (Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair)5 – Death

ECOG Performance Score

JOP September 2014 vol. 10no. 5 e335-e341

Survival in Patients with Advanced Cancer Based on

Performance Score

If the patient has a good response to treatment then survival will be prolonged

Survival with Advanced Colon Cancer Based on the Response to

Chemotherapy

Impact of Response to Chemotherapy on Breast Cancer

Patients by Cancer TypeLuminal- A Type Cancers Triple Negative

Definition and Impact of Pathologic Complete Response on Prognosis After Neoadjuvant Chemotherapy in Various Intrinsic Breast Cancer Subtypes

JCO May 20, 2012 vol. 30 no. 15 1796-1804

Recommended Web Sites from Doctor Miller

The best site would be the NCCN / esp. the patient site: www.nccn.org or www.nccn.org/patients

The next best would be from the NCI (National Cancer Institute) or CancerNet at www.cancer.gov the NCI booklets are very good at www.cancer.gov/publications/patient-education

CancerNet from ASCO (American Society of Clinical Oncology) is very good at www.cancer.net

American Cancer Society at www.cancer.org is good

Finally Doctor Miller’s site at www.aboutcancer.com has a large amount of information and a medical video channel