The research staff at the Dr. Susan Love Research Foundation has recently completed several research studies. Although all of the data has not yet been analyzed, we have several interesting results that we believe will advance our understanding of breast cancer.
On May 4, 2010, we shared some of our findings with our research participants and other invited guests at â€œAn Afternoon of Results,â€ an event held at the Main Branch of the Santa Monica Public Library, which is located near the Foundationâ€™s offices in Santa Monica, Calif. The event was a wonderful informal review of our research collaborations. These were some of the highlights:
Genetic Effects of Early Pregnancy
Dr. Raj Lakshmanaswamy, who is conducting research with the Foundation, came in from El Paso, Texas, to describe the interesting findings from his study exploring the reasons why early first pregnancy (under age 35) decreases a womanâ€™s risk of breast cancer.
Dr. Lakshmanaswamyâ€™s hypothesis is that early pregnancy causes changes in the DNA of the breast tissue that makes it more resistant to cancer. He told the audience how he had thought he would have to do his research in rodents because he would never be able to get human tissue to explore. But then, at a meeting in Washington, DC, he and I discussed his theory, and I told him we could get him the tissue he needed. This led to our collaboration. The Dr. Susan Love Research Foundation collected the blood and core biopsies from three groups of womenâ€”never pregnant, first pregnancy before age 35, first pregnancy after age 35. And Dr. Lakshmanaswamyâ€™s research team did the analysis.
Dr. Lakshmanaswamy told the audience how appreciative he was that women were willing to undergo these biopsies to help his research, and he described how carefully guarded the precious specimens were in his lab. He then explained the relationship between DNA, RNA, and protein. I jumped in with my favorite DNA metaphor: Think of DNA as an ancestral and precious cookbook that you keep under lock and key. When you want to use a recipe to make a cake, you donâ€™t want to risk damaging the fragile book, so you make a copy of the recipe to bring into the kitchen. This is the messenger RNA that takes the recipe to the kitchen/cell and makes the cake/protein.
Dr. Lakshmanaswamyâ€™s research team compared genes taken from the breast tissue from each of the three groups of women and then looked at the DNA, RNA, and protein. They found that there were thousands of genes that were different between the women who had a first pregnancy before age 35 and those who had a first pregnancy after age 35 or who had never been pregnant. They then looked at the RNA to see if all of these genetic changes were actually being translated into protein. The differences remained, but now there were only 47 genes that seemed to be different. Dr Lakshmanaswamyâ€™s lab is now studying these 47 genes. Their goal is to figure out not just what the differences are, but whether there is something that can be done to mimic these protective changes in the genes. The presentation ended with a great slide depicting a picture of each womanâ€™s breast tissue with â€œThank You!â€ written across it. (See photo).
Resting Breast Physiology
Dr. Dixie Mills presented early data from the Foundationâ€™s physiology study. In this study the Foundation is exploring how the resting, or non-lactating, breast functions. A lot of research has been conducted on how the lactating breast functions and what drugs and chemicals are absorbed by the breast ducts and expressed in breast milk. But virtually nothing is known about how the non-lactating or resting breast works and what, if anything, is absorbed by non-lactating breast. It has been proposed that the breast ducts in the resting breast may be like a stagnant pond, with carcinogens bathing the cells that ultimately become cancer.
In this Avon Foundation for Women-funded study, the Foundation explored the hypothesis that pregnancy may change the way the breast functions and what is found in the breast. In order to explore this we studied caffeine and cimetidine (Tagamet), both of which have previously been studied in lactating women. We found that the resting breast was in fact very different from the lactating one. In lactating women, caffeine gets into the breast milk within 15 minutes and cimetidine is concentrated in the milk. In contrast, in the resting breast caffeine takes six hours to get into the fluid while cimetidine does not get into the fluid at all.Â We have also studied several other over-the-counter drugs and we are currently analyzing the results from these studies, and look forward to sharing them with you soon.
Correlation of Anatomy and Physiology of the Breast
I gave the last presentation, discussing the data from the Foundationâ€™s Correlation of Anatomy and Physiology of the Breast (CAP) study. We launched the CAP study so that we could explore differences and similarities between the hormones and cells contained in each breast duct. (It has long been assumed that all the breast ducts were the same. This study was designed to question that assumption.)
For this study, we performed ductal lavage on at least three ducts in a womanâ€™s breast under ultrasonic guidance and then repeated the procedure six months later. More than 100 women participated in this research project. After some initial difficulties with the hormonal analysis, we are now deep into exploring our findings.
The first and most important finding is that each duct appears to be unique. In other words, the estrogen, progesterone, and DHEA levels in one ductÂ differ from those in the other two ducts. This corresponds to our finding that the cells, both in number and degree of atypicality, are unique from one duct to another. It also corresponds to findings from another study we are concurrently conducting that shows that cytokines, or immune proteins in the fluid, are unique to each duct.
This finding that each duct is unique has not been previously appreciated, and it may explain why only one ductal system develops breast cancer. We also have found that it appears that the breast itself may be able to make progesterone. We have known that the breast can make estrogen, but no one has ever previously reported that the breast can make progesteroneâ€”even though the breast has all the appropriate enzymes that are necessary to do so. We are now looking at the ducts themselves through our newly acquired ductoscope to determine whether it can be genetically demonstrated that they are unique. We look forward to updating you on these research results as well.