Lion Dressed Up As Lamb: Breast Cancer in Young Women

By Dr. Kathleen T. Ruddy

“Evidence from the US National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database suggests that the incidence of advanced breast cancer in young women is increasing.”

This is the opening statement in an article just published in the Journal of the American Medical Association.  It should pass as a shot across the bow for women concerned about the overall increased incidence in breast cancer in the United States and everywhere else in the world.  Before I dive into the details of the study, let me define some terms and explain how the investigators collected the data they used to conclude that cases of advanced breast cancer in young women is on the rise, and has been for at least the past 34 years.

The National Cancer Institute collects cancer statistics on approximately 28% of the population. Dr. Rebecca Johnson, Medical Director of Seattle’s Children’s Hospital Adolescent and Young Adult Oncology, and Dr. Archie Bleyer, clinical professor of radiation oncology at Oregon Health & Science University, examined SEER data from three periods:  1973-2009, 1992-2009, and 2000-2009.  Keep these time frames in mind, for improvements in diagnosis of advanced breast cancer and treatment are important factors in any statistical analysis – and these confounding factors were minimized by the investigators by looking at older and more recent SEER data.

Johnson and Bleyer examined information on 936,497 women diagnosed with breast cancer between 1976-2009.  Of these, 53,502 were diagnosed between the ages of 25 and 39.  The authors discovered that these were the only patients whose breast cancer was diagnosed more frequently as advanced, metastatic disease.

Localized breast cancer is defined as malignancy confined to the breast.  Regionalbreast cancer is defined as malignancy that has spread to contiguous organs, such as lymph nodes and the chest wall.  Advanced breast cancer is defined as malignancy that has spread to distant organs (bone, brain, lung, liver, etc.).  This is also referred to as metastatic disease.

Johnson and Bleyer found that the number of women between 25-39 diagnosed with advanced, metastatic breast cancer steadily increased by 2.07% per yearover the past 34 years.

Of course, the incidence of breast cancer has increased in women of all ages over the same time period, but only the youngest cohort showed an increase in diagnosis of advanced disease.

This “almost alarming trend’, as described by Bleyer, was observed in all races and ethnicities, especially in blacks and non-hispanic whites.  The trend occurred in both metropolitan and rural areas.

Furthermore, the type of breast cancer was different than what might be expected in young women:  rather than estrogen receptor-negative (ER-) disease, which is more common in young women, women diagnosed with advanced breast cancer over the past 34 years were more likely to have estrogen receptor-positive (ER+) disease.  This may explain why the overall survival of these young women did not appear to be decreased, as would be expected in patients diagnosed with metastatic breast cancer.  The standard of care is for patients with ER+ breast cancer to receive five years of anti-hormonal therapy with a drug like tamoxifen that significantly increases overall and disease-free survival.

Some critics have suggested that increased screening may explain the increased incidence of advanced breast cancer in young women, but I find that argument ludicrous.  Hundreds of thousands of women under the age of 40 would have had to be screened to find the statistically significant handful of increased cases reported by Johnson and Bleyer.  This simply did not take place!  Young women with a strong family history of breast cancer, and those who are known to be BRCA mutation carriers, would certainly have been screened at an earlier age – but that doesn’t explain away the findings of a widespread increased incidence of advanced, aggressive breast cancer in all races and in all regions of the country reported in JAMA this week.

Bleyer claims that this is the first report of such a trend.  But he’s wrong.  This trend – young women with advanced ER+ breast cancer at diagnosis – has been seen in the Gulf and Middle Eastern countries for years.  I discovered this very strange pattern of breast cancer in 2006 when I first visited Kuwait.  I verified it using statistics obtained from the Kuwait Cancer Center.  A regional breast cancer conference convened by the Ministry of Health of Kuwait in 2007, confirmed  that this strange pattern of breast cancer was also being reported  in other countries in the region.  On a more recent visit to the area as an invited speaker for the University of Michigan Global Health Network meeting on Cancer in the Gulf and Middle East convened in September 2011, all countries (Egypt, Saudi Arabia, Lebanon, Quatar, etc.) reported the same thing:  advanced, aggressive, ER+ breast cancer in young women.  Bleyer has made inquiries of his colleagues in Canada, but he might want to take a trip to the Gulf, Middle East, and northern Africa to discuss this strange form of breast cancer with researchers there.

Here’s my question:  what is causing this peculiar form of aggressive, ER+ breast cancer in young women anywhere in the world?

And is the pattern of advanced, aggressive breast cancer in Gulf countries similar to the the advanced, aggressive, ER+ breast cancer we are seeing in increasing numbers here in the United States?

And is there any relationship between these patterns and the increased incidence of breast cancer now being reported in young female veterans who have served in the Gulf Wars?

Isn’t it time to connect some of these dots?

We have the technology to study the genetic pattern of this peculiar form of breast cancer.  We have the financial means to compare these cases between countries:  we spend at least $50 billion on breast cancer in the United States alone.   If we can trade oil, send troops, fight wars, and ship cell phones across the pond, we can certainly share data about advanced, aggressive, ER+ breast cancer in young women here, in the Gulf, in northern Africa, and in the Middle East.

We have the means, but do we have the will?   The editorial review board of JAMA thoroughly vetted the data submitted by Johnson and Bleyer.  They found that the likelihood that their results were due entirely to chance to be less than 1 in 1000.  It’s fair to say that what’s reported is true.  The incidence of aggressive, advanced ER+ breast cancer in increasing here and, very likely, elsewhere in the world.

King Henry:
Once more unto the breach, dear friends, once more;
Or close the wall up with our English dead.
In peace there’s nothing so becomes a man
As modest stillness and humility;
But when the blast of war blows in our ears,
Then imitate the action of the tiger. . . .

Henry The Fifth Act 3, scene 1, 1–6

Who will join me?

Reference:  JAMA, 2013; 309(8):  800-805