Clue found in aggressive breast cancer
September 28th, 2010
03:55 PM ET

Clue found in aggressive breast cancer

Researchers may have found a new lead toward  treating triple negative breast cancer, a rare and aggressive form of the breast cancer that occurs more often in younger women and African-American or Hispanic women.

A study looks at insulin-like growth factor 1 receptor (IGF-1R), which has been shown to be involved in several cancers, including more common types of breast cancer. But no study has focused on its role in triple negative breast cancer before. The findings were presented at the Fourth AACR International Conference on Molecular Diagnostics in Cancer Therapeutic Development on Tuesday.

"There is a desperate need to better understand this cancer and find potential new targets for treatment," said study author Dr. Agnieszka Witkiewicz, associate professor of pathology at Thomas Jefferson University Hospital in Philadelphia, Pennsylvania.

There are about about 207,090 new cases of invasive breast cancer in women each year in the United States, according to the latest information from the American Cancer Society. Between 10 to 20 percent of breast cancers are triple negative, according to breastcancer.org.

Receptors are proteins on the surface of cells which receive signals to grow. Specific types of receptors on cancer cells indicate what is fueling the cancer.

The diagnosis of most breast cancers involves three types of receptors: estrogen receptors, progesterone receptors and human epidermal growth factor receptor 2 (HER2). But in triple negative breast cancer, estrogen and progesterone receptors are not present in the cancer cells, and there is not an excess of the HER2 protein on the cells' surfaces.

That means that patients with triple negative breast cancer will not respond to treatments targeted at those receptors. Chemotherapy can help, but this is form of breast cancer often takes an aggressive course, and has a high likelihood of recurrence.

Witkiewicz's study showed that IGF-1R was overexpressed, or present in excessive amounts, in 25 percent of cases, meaning this protein could be a potential therapeutic target. Participants included 73 white and 24 African American patients.

Overexpression was associated with longer survival in patients under 55 years old. This high expression was somewhat associated with low tumor size; low expression carried a greater risk of lymph node metastasis.

There are already several clinical trials involving drugs called IGF-1R inhibitors that could be relevant for triple negative patients, based on the findings of this study, Witkiewicz said. After more patients are analyzed, researchers could look at clinical trial data to see if the response to the drugs is associated with IGF-1R overexpression. In other words, this particular protein may be predict how well a patient responds to drugs in clinical trials.

In most studies of breast cancer, patients with triple negative are underrepresented, she said.

soundoff (23 Responses)
  1. James Michael Howard

    It is my hypothesis of 1994 that increased testosterone increases breast cancer, as well as other cancers, (International Journal of Cancer 2005; 115: 497). It has been determined that testosterone increases IGF-1 receptor "abundance" (Endocrine. 2001 Oct;16(1):1-6).

    I suggest the connection regarding increased IGF-1 receptors and breast cancer, just reported by Witkiewicz, et al., at the Conference on Molecular Diagnostics in Cancer Therapeutic Development on Tuesday, may be directly related to my hypothesis, as well as the findings that IGF-1 receptors are increased in other types of breast cancers / cancers.

    It is also my hypothesis that the percentage of women of higher testosterone are increasing with time within the population and this increase is the cause of the increase in breast cancer with time within the population. (This increase in women of this type may be the basis of the "secular trend," and may also be the basis for the consistent, parallel increase in breast cancer, obesity, diabetes, etc. that are increasing simultaneously.)

    James Michael Howard
    Fayetteville, Arkansas

    September 29, 2010 at 08:21 | Report abuse | Reply
    • Arla

      First, I agree with Tina, this is about life and death and should not be taken so lightly.....Women are dying every single day from this. I am a triple negative breast cancer patient that had a bilateral mastectomy one year ago and this is very encouraging indeed. Mr Howard, I am interested in learning more about your research please!

      September 29, 2010 at 11:31 | Report abuse |
    • Carmella

      My sister was diagnosed with triple negative breast cancer. She will turn 40 on December 23rd this year. She has three daughters. She had a historectomy about a year ago and was not taking hormones of any kind. Her father is white and her mother is native american and spanish mix. She had test ran to see if her cancer was genetic and they results were negative. Okay knowing all those factors – your hypothesis is not accurate in her case.

      September 29, 2010 at 12:02 | Report abuse |
    • Kay

      I was diagnosed with triple negative breast cancer a year ago, and was in a relationship with a man who was taking testosterone pellets, and using testosterone cream for 8 years. Could there be a connection?

      September 29, 2010 at 15:54 | Report abuse |
  2. Bob

    Well, Mr. Howard – testosterone being the only known hormone to help a woman's sexual libido now increases their risk of developing breast cancer. Ain't that just great. It appears that God just doesn't want women to have pleasure at all.

    September 29, 2010 at 08:48 | Report abuse | Reply
  3. tina

    Please KNOCK off any rude, comments or remarks...Breast cancer IS NOT to be taken lightly in any way, shape or form...I know I had both breasts removed last year cause of this disease and any one who hasn't went through breast cancer themselves, has NO idea what a person goes through sexual, emotional, physical. this disease affects soooo much of ones life it is indescribable.l

    September 29, 2010 at 09:27 | Report abuse | Reply
    • Ames

      Tina...so glad you made it through and are here. Blessings to you and your family.

      September 29, 2010 at 10:24 | Report abuse |
  4. Kay

    I was diagnosed with triple negative breast cancer a year ago, and was in a relationship with a man who was taking testosterone pellets, and using testosterone cream for 8 years. Could there be a connection?

    September 29, 2010 at 11:42 | Report abuse | Reply
  5. Ryan Serra

    I find this article a little confusing. I am currently finishing my PhD and I work on a variety of cancers including breast cancer so I would say I am at least fairly familiar with the field. So IGF1R is a known tumor suppressing gene in many cancers. There are many lines of evidence that supports this including being suppressed in advanced tumors, overexpression of IGF1R reduces tumor growth in cell line models and I could go on an on; all of which can be found in the scientific literature.

    BUT, this study finds the same thing, it is overexpressed in a small subset of breast cancers. The patients with overexpression have increased survival, reduced tumor size etc. which supports its role as a tumor suppressor. Yet the end of the article talks about inhibiting the function of IGF1R which I think is opposite of what we should be trying to do. Instead we should be activating the gene so that it can suppress or kill the tumor.

    I only bring this up because I co-discovered a protein in the body that uses IGF1R to kill melanoma cells. (you can google my name, Serra RW, and the gene is IGFBP7 in Cell magazine, however the work about how IGFBP7 uses IGF1R as a receptor isn't published yet). I would think that activating IGF1R would be a more logical approach and anyone who has cancer in general but more specifically, triple neg. breast cancer should avoid IGF1R inhibitors. I'm not a MD, so don't go against your own Dr.'s orders but as a scientist, I'd say this article kind of gives the wrong impression at the very end.

    September 29, 2010 at 18:35 | Report abuse | Reply
    • Midwestmatt

      I sent this article link to a woman who was recently diagnosed with triple negative BC in Phoenix. She had radical mastectomies of both breasts as a preventative measure and has undergone both chemo and radiation. She is 47 or 48 years old.

      She, too, did not understand the conclusion of this article and if anyone can clarify the findings, it would be greatly appreciated.

      September 29, 2010 at 23:23 | Report abuse |
    • MJ

      Midwestmatt, maybe this will help. First, while the press release (which is poorly written and explained) did not state it, these patients were likely treated with chemotherapy after the biopsy (tissue used to diagnose cancer and also used here to measure IGF1R) which is standard for triple-negative breast cancers. While patients with high IGF1R levels had a better prognosis this doesn’t mean that they all survived just that they survived longer (possibly only a few months). There is a huge amount of data demonstrating that IGF1R causes tumor cells to grow rapidly. Since chemotherapy kills rapidly growing cells patients with high IGF1R likely responded better to treatment and that’s why they had a better prognosis. Keep in mind that estrogen receptor positive breast cancers also have a better prognosis. This is due to the fact that the tumors aren’t as aggressive (but still kill) and can be treated with anti-estrogen therapies such as tamoxifen. Hope this helps!

      September 30, 2010 at 11:35 | Report abuse |
  6. Linda

    I was also diagnosed with triple negative breast cancer metastisis. biopsy was done in clavicular area in May and lymph nodes under my left arm were also enlarged in May 2010. Since taking vitamins and supplements. plus exercise daily I am healthier and the swollen nodes have reduced in size significantlly. I have been eating healthier as well– 5 servings of organic vegetables per day, 2 organic fruits and cutting out refined sugar in foods. Instead use agave for sweetner or honey. I have been taking 500 mg (6 per day) of Vitamin C daily, 200 mg selenium, 200 mg CoQ10, Vitmain E- 400 mg, Indole 3 carbinol, calcium 500 mg 2 times daily, 5,000 iu of Vitamin D; 1 tsp of Turmeric per day; 4 cups of Green tea, others supplements are taken interchanged each week: mushroom extracts, echinacea, and astragalus root extract.
    I feel that I am killing this cancer and my energy level has been great. Also, Accupture and chiropractic adjustments are also helping me. I have never done chemotherapy because I do not feel killing all my good cells makes any sense for me to heal my cancer.

    September 29, 2010 at 23:25 | Report abuse | Reply
  7. Cancer

    Check out the NCCN Breast Cancer Guidelines for their recommendations http://www.nccn.com

    September 30, 2010 at 10:27 | Report abuse | Reply
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    Hormone disbalance is a key factor in mood swings, hot flashes, of course the onset of menopause for women as well as men. These comments are related and helpful.

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