Risk Factor

A risk factor is anything that increases your chances of getting a disease.

But, having a risk factor, or even many, does not mean that you are sure to get the disease. While

you can’t change some breast cancer risk factors—family history and aging—there are some risk

factors that you can control. (not a complete list but most of the big ones)

• Drinking alcohol is clearly linked (something that definitely surprised me was how much)

• 1 drink/day, "7-10% increase"

• 2-3 drinks/day,  "20% increase"

• Obesity Numbers are less clear. and, oddly, it’s different if weight is gained after menopause (worse)

• Sedentary lifestyle (conversely, exercise helps lower risk)

• Not having children/ not breastfeeding

• Birth control with estrogen

• Menopausal hormonal therapy ​

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--Breast implants, by the way, are NOT linked to increase risk, though it can be harder to detect cancers with mammograms.

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If I had to summarize the above modifiable risk factors, they all are related to estrogen.  Even when not obvious.  e.g. fat produces estrogen.  Also, when pregnant or breastfeeding estrogen cycles are reduced.  Less cycles, surges of estrogen, then less lifetime amount .

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I wish to point out again, however.  Having a risk factor does not mean that getting breast cancer is inevitable.  Even that 10% increase just means you have gone from roughly a 10% lifetime risk to an 11% lifetime risk.  

Most surprising to me is that smoking is not highly linked.  The U.S. Surgeon general concluded in 2014 after looking at numerous studies that there is ‘suggestive but not sufficient evidence of a link’ between smoking and breast cancer risk.   

​Risk factors that you can’t change

Being born female.  But it must be stated that men can also get breast cancer.

• Women 12.9% lifetime risk      Men 0.13% lifetime risk

• Getting older.  The chance increases with each decade of life.  

  30’s  0.49%
  40’s 1.55%
  50’s 2.40%
  60’s 3.54%
  70’s 4.09%

• Specific genes.  It’s felt that 5-10% of breast cancer is hereditary (conversely this means the vast majority is just random).  Most linked are the following genes:  BRCA 1, BRCA 2, ATM, PALB 2, TP53, CHEK2, PTEN, CDH 1, STK 11

• Family history of near relative (mother, sister, daughter).   Having any of these doubles lifetime risk from approximately 10 to 20%.  Having two or more relatives increases risk 2 to 4 times.

• Race—Asian, Hispanic and Native Americans have a lower risk of developing and dying from breast cancer

• Being taller (I’ll admit this was something I learned).  Not clear why.  Women who are 5’9 or taller have a 20% greater likelihood compared to women 5’3 or smaller. 

• Having dense breasts 

• Early menstruation, Late menopause—again longer exposure to estrogen.  

Screening

I’ll start by saying there are numerous guidelines which are different.  And, all discussion below is based on women with AVERAGE RISK.  (If you wish to get an idea of your risk, there are many models to choose from. Perhaps the most known is the Gail model.  There is an easy tool on the internet I found from the NIH  (https://bcrisktool.cancer.gov/calculator.html) A big reason for this difference is the goal.  Is the goal to detect cancer early or is the goal to prevent death?  Why this matters is because if treatment has improved so much that you don’t die from breast cancer (5 year survival rates that were 75% in 1975 have increased to over 90% currently), early detection becomes less important.  Or put another way, less statistically significant.  A spectacular YouTube video regarding this is by Vinay Prasad—does mammography save lives?

Below are current guidelines for mammography from different sources.  

The United States Preventative Services Task Force (USPSTF)

•  Grade C recommendation for Mammograms between ages 40 to 49

• Grade B recommendation for Mammograms between ages 50 to 74

• Insufficient Evidence to recommend for or against after age 75

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Available observational evidence evaluating the effects of varying mammography intervals found no difference in the number of breast cancer deaths between women aged 50 years or older who were screened every year versus every other year.

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American College of Gynecology:

• Basically, the same recommendations as above.

Canada:  

• Not recommended ages 40 to 49

• Every 2-3 years between 50 to 74

Europe:

• Every 2-3 years ages 50 to 70

What all women should know about mammograms—The Bi-Rads category.  It is a way of grading your mammogram.  It’s helpful because when you see this number on your mammogram you can get an idea of the concern—especially when you are asked to come back for more imaging which can be very scary.  

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1—Negative; nothing found:  the risk of cancer diagnosis within 1 year is 1%  Follow up in 1 year
2—Benign; the risk of cancer diagnosis within 1 year is 1%  Follow up in 1 year
3—Probably benign; the risk of cancer diagnosis within 1 year is 2%  Follow up in 6 months.
4—Suspicous; Likely requires biopsy.  The risk of cancer diagnosis within 1 year is 
4a: 2-10%
4b: 10-50%
4c: 50-95%
5.—Highly suggestive of malignancy; the risk of cancer diagnosis within 1 year is 95%
6—Known biopsy-proven malignancy

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Also, women should be clear about how much radiation they are getting—very little. Just radiation from the sun gives us all about 3 milliSieverts each year.  A mammogram gives 0.4 milliSierverts.   How big of a risk is this and…how did we figure this out?  It’s just not clear because much of our data is inferred by what happened to victims of the nuclear bombs in Hiroshima and Nagasaki.  But for context it is believed that if you get more than 1,000 milliSieverts you increase your risk of fatal cancer by about 4 to 5 percent.  Doing the math, you would need about 2,500 mammograms to achieve this level.  

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Breast implants.  These can hide breast tissue making it more difficult for the radiologist to detect breast cancer.  However, the above screening recommendations don’t change.

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What is 3D Mammography?   This is like a CT scan of the breast versus an X-ray.  The X-ray (mammogram) is 2 dimensional.  The 3D version, also known as digital breast tomography (DBT) uses a computer to analyze slices of tissue.  It’s not clear if this mode can improve outcomes.

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For average-risk women, there is a lack of medical evidence to routinely recommend other imaging modalities or supplemental screening with Ultrasound, Magnetic Resonance Imaging (MRI), or newer imaging technologies.

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Breast self exam (BSE).  This was recommended in the past and now is actually discouraged.  It has been found that it detected primarily benign disease and led to more biopsies without any benefit.   But I think this recommendation is curiously discussed.  YES, if you feel a lump/ mass in your breast you should definitely seek the attention of a clinician.
 

BREAST CANCER TREATMENT

Surprising to me was the percentage of cancers found in the early stage—not yet metastasized.  Approximately 95% of women who are told they have breast cancer have local disease.

This is further broken down to two stages:  

• Early stage   1, 2A or some 2B cancers

• Locally advanced stage    2B (that are T3 N0), stage 3

This staging system is complicated and so I won’t go through it all here.  I think easiest to just compare ‘early’ vs. ‘locally advanced’ stage

EARLY STAGE—Remove the cancer with surgery is the primary goal (lumpectomy or mastectomy)

Then, based upon risk factors as well as tumor characteristics, adjuvant treatment is discussed.  This is either Tamoxifen or an Aromatase inhibitor typically for Five years.

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What does ER positive, PR positive, HER positive mean?

• ER stands for estrogen receptor.  This implies that the breast cancer is ‘responsive’ (grows faster) when exposed to estrogen.

• PR stands for progestin receptor.  Similarly, the tumor would grow faster when exposed to progestin.

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Which of course means the converse is true.  Without estrogen/ progestin, the tumor will grow less well.  When Pre-menopausal, there is a lot of estrogen/ progestin around.  The standard treatment is known as TAMOXIFEN.  This oral treatment blocks the estrogen receptors.  Yes, your body still makes estrogen, it just can’t, in the presence of Tamoxifen,  activate/ make the cells grow faster.  It works great with two main concerns.  1. It instantly puts a woman into menopause   2. It slight increases the risk of uterine cancer.

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Post menopausal women are making very little, if any, estrogen from the ovaries, but there is a conversion to estrogen, primarily from fat and androgens in the body.  The AROMATASE INHIBITORS block the conversion of androgens to estrogen.  Examples of these drugs are Anastrazole, Letrozole and Exemestane.  Also, these have several side effects which include:  Joint pains, menopausal symptoms and thinning bone.

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Human Epidermal growth factor Receptor 2 (HER2).  Though a little more complicated, the bottom line is the same, if the tumor expresses these receptors, it will grow more slowly if blocked.  To do so, Trastuzumab is the drug of choice.  

LOCALLY ADVANCED BREAST CANCER.  This is defined as an inoperable breast cancer without distant metastases.   More simply put, just removing the cancer is not likely to prevent recurrence and cancer spread.  Something else must be done.  This is typically done before surgery and known as NEOADJUVANT therapy.  Chemotherapy or Immunotherapy is done to decrease the size of the tumor and only after this is surgery performed to remove the breast lump.

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After this, SURGERY, is typically performed.  The choice of lumpectomy vs. mastectomy is influenced by many things including how well the tumor responded to the neoadjuvant therapy.

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ADJUVANT therapy, is what is done after surgery to prevent recurrence of the disease.  There are so many choices for this, but are typically broken down into Hormonal regimens, Immunotherapy or Chemotherapy.  Hormonal therapy we discussed above.  Chemotherapy we inherently know are medicines used to help slow down cancers more so than our own cells.  But I’d like to discuss Immunotherapy a little as this is somewhat new.

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IMMUNOTHERAPY—The idea behind this is that our immune system wants to attack and destroy foreign things such as bacteria.  In fact, it was the surgeon Dr. William Coley in the 1890’s who injected killed bacteria into a tumor and showed that it shrank.  Truly genius.  Getting our own body to attack the bacteria and, by extension, the tumor.  He was inspired by an amazing case.  A German immigrant named Fred Stein came to New York hospital with an inoperable tumor of his neck. Then, he developed a skin infection at the site.  Soon after, the cancer went away completely. Dr. Coley theorized that his own immune system must have attacked and killed the cancer.   Putting this theory into practice a year later he injected live streptococcus bacteria into a tonsillar cancer of an Italian immigrant named Zola.  After just two weeks her cancer resolved.  She lived another 8 years.

Unfortunately, treatment is nowhere near so simple with breast cancer.  But there is a role, most commonly for the tumors that are known as Triple Negative.  ER negative, PR negative and HER2 negative.   In other words, they aren’t slowed down by anti-hormonal techniques.  I mentioned on earlier, Trastuzumab with regards to those who are HER2 negative.  They also will use Pembrolizumab.  These monoclonal antibodies (you can always tell as their name ends in MAB which stands for Monoclonal AntiBody) are used most often with breast cancer.  

The big study with Trastuzumab was a 10 year study of 14,000 women.  They compared women who were HER2 negative receiving either chemotherapy alone OR chemotherapy plus Trastuzumab.  After 10 years the difference was felt to be a great success

• recurrence of breast cancer 31.9% vs 22.9%

• breast cancer mortality 21.1% vs. 14.7%

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There are a tremendous number of trials and numbers I could write about here.  I feel it would just be confusing.  I wrote about this study with Trastuzumab to illustrate how we can look at numbers to make decisions.  But I do wish to point out something very important.  We should look at the numbers that are being proposed and then decide whether the benefits outweigh the risks for YOU.  In general, with such good numbers as noted above, I tend to recommend trying the treatment that is proposed.  Then, and only then can you learn of your side effects.  If they are acceptable, then keep on going.  In the end, we judge things based on benefit vs. risk.  Much of the risk we face with these treatments is based upon side effects of the medications which only you will know.  

I hope this summary was helpful.  It truly is an incredibly large topic.  My goal is that now you are more aware of the decisions you have to make regarding screening.  And, that you know a little more on how to discuss with your friends or family this topic which is, sadly, so common.