Jean, and others who have asked me for an article on the relative merits of the diff-

[Lani]

rent AIs:

The Breast Journal
Volume 15 Issue 2, Pages 194 - 198
Published Online: 9 Mar 2009


SHORT COMMUNICATION
Enhancing the Adjuvant Treatment of Hormone Receptor Positive Breast Cancer
Mitchel Barry, MD, MRCSI and Malcolm R. Kell, MD, FRCSI
Breastcheck, Mater Misericordiae University Hospital, University College Dublin, Dublin, Ireland
Address correspondence and reprint requests to: Malcolm R. Kell, MD, FRCSI, Breastcheck, Mater Misericordiae University Hospital, University College Dublin, 36 Eccles St, Dublin, Ireland, or e-mail: malcolm.kell@breastcheck.ie
KEYWORDS
aromatase inhibitors • optimum adjuvant treatment • anastrozole • letrozole
ABSTRACT
Abstract: Aromatase inhibitors (AIs) are now regarded as the optimum hormonal therapy for postmenopausal women with hormone receptor positive breast cancer. However, it is unclear which of the currently available AIs offers patients the most effective and the best-tolerated treatment strategy. We performed a systematic review and meta-analysis of randomized-controlled trials that compared AIs (as first-line agents) with standard hormonal treatment in patients with breast cancer. The results suggest that letrozole offers a more favorable side-effect profile particularly in terms of musculoskeletal adverse events. However, the available data suggests a small survival benefit from the use of anastrozole although patients treated with anastrozole appear to have a more favorable disease profile at study entry. Examination of survival data on adjuvant tamoxifen therapy from these trials supports this observation.

[Hopeful]

Lani, this is interesting, as Letrozole (Femara) is a more potent suppressor of aromatase than Anastrazole (Arimidex). Could it be the metabolization of the drug, rather than the absolute value of circulating ER achieved, that is the difference? If so, it would mean a lot to those of us using topical estrogens to combat the side effects of the AIs.

Hopeful

[Lani]

the level of the bc cell which may make (or its surrounding stoma makes) their own hormones:

GUMC Researchers: Test for Hormones in the Blood Not Reflective of Hormones in Breast Tissue; Breast Cancer Risk

Denver, Colo. – Many studies determine hormone levels in the blood as a marker of breast cancer risk. But it hasn’t been known whether these blood tests reflect what is happening in the breast tissue, where certain hormones fuel cancer. Researchers at Georgetown University Medical Center’s (GUMC) Lombardi Comprehensive Cancer Center found that measuring the levels of four hormones in blood known to be linked to breast cancer doesn’t necessarily reflect the levels of these hormones in the breast tissue itself.

In fact, the scientists say that blood tests used in research studies that measure these hormones could give a false impression of both the real breast cancer risk women face, and an imprecise picture of how these hormones affect breast cancer development. The findings are being presented at the Annual Meeting of the American Association for Cancer Research.

“We know from this study that measuring the hormones in a patient’s blood is not sufficient but that is how many research studies looking at breast cancer risk are being conducted,” says the study’s lead author, Adana Llanos, a graduate student in genetics at GUMC. “Understanding how cancers develop in breast tissue is the key to prevention, and we need to understand how these hormones affect breast tissue.”

The research team, led by Llanos and under the guidance of senior investigator, Peter G. Shields, MD, head of Lombardi’s Cancer Genetics and Epidemiology Program, did something that has not been done before: They tested normal breast tissue for the levels of IGF-1, IGFBP-3, adiponectin, and leptin. High levels of IGF-1 has been linked to breast cancer development, while low levels of IGFBP-3 is linked to increased risk. High levels of adiponectin and leptin are both related to obesity, which is, in itself, a risk factor for breast cancer.

“By understanding these hormones in the normal breast environment, we will have some insight into how early changes in the breast lead to breast cancer,” Llanos says. The researchers asked 15 women who were undergoing breast reduction surgery to participate in the study, and then collected three samples of discarded tissue from each breast, as well as blood, and extensive epidemiological data.

They first assessed whether levels of these hormones were the same in each of the three tissue samples taken from the women, which represented different areas of the breast. “We found that the hormones were distributed in the same way across the breast, which is a good thing to know because it means that a tissue biopsy taken from one part of the breast will likely represent the breast as a whole,” says Llanos.

They then tested the blood to see if levels of the hormones matched those found in the breast tissue, and found that leptin, adiponectin, and IGFBP-3 correlated, whereas IGF-1 did not. But even that may be misleading, Llanos says, because hormone levels may differ between a woman’s two breasts. “Breast cancer usually develops in a single breast, so it is not clear that looking at these hormones in the blood is sufficient,” she says.

“If we want to know what is occurring in the breast, then we have to go to the tissue itself,” Llanos says. “Measuring blood would be more convenient, but our study shows that, alas, this may not be accurate.”

Llanos and her co-authors report no related financial interests. This work was funded by a grant from the Department of Defense.

[Hopeful]

This is the statement that is fascinating to me:

"But even that may be misleading, Llanos says, because hormone levels may differ between a woman’s two breasts. “Breast cancer usually develops in a single breast, so it is not clear that looking at these hormones in the blood is sufficient,” she says."

So, the million dollar question is, why are gene changes limited to one breast and not the other? Or why do excess hormones collect in one and not the other?

I like things that make me think!

Hopeful

[StephN]

In the case of a patient who is triple negative, could the above findings be why that person might be given Tamoxifin???

Lani - I met a Chinese researcher at AACR who works in this country and whose wife was diagnosed last summer with breast cancer, triple negative. He said she had surgery and was being given tamoxifin. He was very worried about all that and seemed to find that he could speak with me about his fears.

I was a little puzzled about the treatment he outlined for his wife.

[Jean]

Thank you Lani, I appreciate your attention.

Hopeful,
I understand your thoughts - and in thinking about
the breast and the difference of hormonal levels in each one...like any other apendage of our body, such as our legs, one leg could have a cancer tumor while the other leg would not be involved. Maybe I am making it too simple in thought...but I have always felt that each breast is independent of the other in hormones, as I noticed when breast feeding there would be more available milk sometimes in one breast verses the other,
does this sound crazy?

jean

[Hopeful]

Jean,

I have no children so have never breastfed, making your observation interesting to me. I think that the entire realm of endocrinology is overlooked in bc; it would be endocrinologists that might have some insight into the hormonal workings ofour tissues, one would think. To answer your question, it does not sound crazy to me. I am just genuinely curious as to how this whole hormonal thing works. I want to see more research conducted such as that which produced this article Lani posted. If doctors are designing clinical trials for bc drugs based solely on blood levels of hormones, and the blood levels are not relevant when compared to the breast tissue, it says to me a lot of the studies don't mean what the researchers thought they meant when they designed them. We all need better information about how these drugs work if we are going to make them work for us.

Hopeful

[Jean]

Hopeful,
Very true...There is still much unknown about AI's
the dr. at first thought a 5yr treatment was sufficient
now that is being expanded. It seems at times we learn as we go.

jean

[Hopeful]

Jean,

I recall reading two years ago about a concept for an AI that would specifically target the ER in the breast, which seems to be what is needed here. I have been disappointed not to see anything further on this; perhaps the research Lani has posted here will renew interest in it. Such a drug would be a huge boon to ER+ bc patients, allowing us to keep our bones (and our sex lives) intact while delivering the tx we really need.

Hopeful

[Becky]

If it is what we really need. I concur with Jean on the differences between the 2 breasts which is really obvious if you breast feed. Ironically my cancerous breast was the better behaved during that process with all 3 children. It made more milk, pumped more easily and it must have drained better because I got mastitis on the other side on the upper outside quadrant (2 different times with 2 different babies).

However, one has to take into consideration that hormone replacement therapy and being overweight (on the premise that fat produces estrogen) does increase bc rate due to increased circulating estrogen.

The second breast theory may have something and it may be just bunk. From my situation, I was diagnosed with a simultaneous IDC on right and dcis on left. Perhaps if my dcis was just atypical hyperplasia, would I have gotten dcis since I was on tamoxifen and then Arimidex. I think you might see my point, once we get a hormone positive bc on one side, if anything was brewing, antihormone therapy is known to assist this situation. Tamoxifen (and probably soon AIs) is given to high risk women who never had bc and it statistically reduces bc rate for those who take it. So, in some sense, of course the unaffected breast has a better chance of being "saved" after a hormone positive diagnosis. It is not foolproof as we all know and we need to be diligent if we have one or both breasts left but antihormone therapy greatly reduces the chance of recurrence or the development of another hormone positive bc.

[Hopeful]

Becky,

I agree with you that endocrine therapy prevents additional hormone positive bc, but, IMO, longer duration therapy (past 5 years) with currently available treatments which affect all estrogen in the body, should be reserved for those patients at high risk. Prolonged estrogen deprivation comes with huge QOL effects. There has to be a balance. An unanswered question is what are we trading off to pursue this treatment? Osteoporosis and vascular disease down the road? A chance at ever again experiencing normal physical intimacy? We need to see overall survival stats, not just disease free survival stats, to answer that question before we consent to 10 years of treatment. Targeted ER therapy that would spare the rest of the body that needs ER to function normally would be a huge boon, would allow for longer treatment durations, and, I am certain, would greatly increase patient compliance with the drugs, which is key to success with them.

Hopeful

[Becky]

I agree. However, I wonder if estrogen supression in the breast would be good enough if circulating estrogen is at some critical point. Also, the idea probably wouldn't be possible in a premenopausal woman since there is so much circulating hormone that it probably could not be overcome.

The idea is excellent for prevention of bc or prevention of local recurrence. However, the idea wouldn't work to prevent distant mets - that sneaky cell that lies dormant in your hip bone. And for me, that potential cell overrides everything. A new dcis, I could take. A recurrent lump on my lumpectomy scar line I could take. I wouldn't be happy and I would be upset. But I don't want some sneaky cell that might be in my lung or liver or bone to get an opportunity. So, for me that means systemic treatment with an AI. The quality part I can work on diligently in many manners if I am alive to do so.

[Hopeful]

Becky,

We all have to make decisions with the information we have. You have weighed the pros and cons as we currently know them and have determined that extended hormonal treatment confers a benefit that outweighs the risk of present and future side effects. Only you can make that choice for you. I don't perceive the situation in the same way, and need to see additional information to be convinced. I think there are significant toxicities to these drugs for which evidence of greater benefit than we are currently aware of for use beyond five years will be necessary for me to pursue that course of treatment - my choice for me. Neither choice is right or wrong. Thank goodness we have a choice.

Hopeful

[Hopeful]

Elsevier Global Medical News. 2009 Apr 20, MG Sullivan


WASHINGTON (EGMN) -Aromatase inhibitors are associated with small but significant levels of additional bone loss in osteopenic women who take the drugs for hormone-sensitive breast cancer, according to a study of 104 women.
After just 1 year of aromatase inhibitor therapy, these women lost a mean of 1.5% in bone mineral density (BMD) at the lumbar spine and 2% at the femoral neck; two of the subjects progressed from osteopenia to osteoporosis, Dr. Pamela Taxel reported in a poster session at an international symposium sponsored by the National Osteoporosis Foundation.
Expected bone loss associated with natural progression generally would be about 0.5%- 1% per year, according to Dr. Taxel of the University of Connecticut Health Center, Farmington.
She and her colleagues performed a chart review of 104 women who were taking the drugs for breast cancer and were evaluated for bone health. Of these, 61 (58%) had osteopenia. The patients' mean age was 58 years; they had been on aromatase inhibitor therapy for up to 2 years. Eighteen percent (11 patients) were taking a bisphosphonate at baseline. They were followed for an additional year.
Lumbar spine BMD measurements were available at baseline and at 1 year for 39 women. After 1 year, the women had lost a mean of 1.5% in BMD at this site; 18 women had lost more than 3%. Baseline and 1-year femoral neck BMD measurements were available for 36 women. After 1 year, there was a mean BMD decrease of 2% at this site. Four women lost more than 3% at the spine and more than 5% at the femoral neck.
Two of the 36 women with both lumbar spine and femoral neck data progressed to osteoporosis during the follow-up period.
The progression in bone loss occurred despite increased compliance with vitamin D supplements. At baseline, 74% were taking at least 1,000 mg/day of vitamin D, although 41% were still deficient. At the end of the follow-up period, vitamin D intake had significantly increased, with only 25% still deficient, Dr. Taxel noted.

Hopeful