Last Updated: 2008-04-01 11:17:07 -0400 (Reuters Health)

Developing anemia during chemotherapy to treat early-stage breast cancer seems to affect the risk of the cancer coming back. The small study reviewed here found that women who became anemic while getting chemotherapy after early-stage breast cancer surgery were more than twice as likely to have the cancer come back 5 years after surgery compared to women who didn’t develop anemia. Almost 20% of the women with chemotherapy-related anemia had the cancer come back 5 years after surgery compared to only 8.9% of the women who didn’t develop anemia.

Many women in the study were followed for more than 5 years. The researchers found that the women in the study who developed anemia had a risk of the cancer coming back at any time (including longer than 5 years after surgery) that was almost 3 times greater than the women who didn’t develop anemia.

Although the risk of the cancer coming back in the breast was different, the researchers found that the risk of the cancer coming back in another place in the body (metastatic cancer) was the same for women who did and didn’t develop anemia. Also, the risk of dying from breast cancer was the same for women who did and didn’t develop anemia.

Chemotherapy is commonly used after early-stage breast cancer surgery to lower the risk of the cancer coming back. Anemia is a common side effect of chemotherapy, but not all women who get chemotherapy develop anemia. Radiation therapy is also used to lower the risk of the cancer coming back when a woman has lumpectomy instead of mastectomy. In addition to chemotherapy, the women in this study got radiation therapy if they had lumpectomy.

The researchers aren’t sure why the women who developed chemotherapy-related anemia were more likely to have the cancer come back.

Doctors sometimes use medicines to prevent or treat chemotherapy-related anemia. This research didn’t look at whether these medications could lower the risk of the cancer coming back. Even with these medicines, many women will still develop some level of anemia, which could affect their risk of the cancer coming back.

If you’re getting chemotherapy after surgery as part of your treatment plan for early-stage breast cancer, talk to your doctor about anemia and steps you can take to lower both the risk of anemia and the cancer coming back. Visit the breastcancer.org Chemotherapy section to learn more about chemotherapy and its side effects.

By Nicholas Mulcahy, HealthDay ReporterTHURSDAY, April 3 (HealthDay News) — Breast cancer patients who develop anemia during chemotherapy face almost three times the risk of a recurrence in the same area of the affected breast, new research suggests.

The Austrian study was a re-analysis of information from a clinical trial that took place in the 1990s. Importantly, the findings also indicated that anemia did alter overall survival or significantly increase the risk of cancer occurring in a patient’s other breast or spreading elsewhere in the body. Anemia, a common side effect of chemotherapy, is a low red blood cell count that can cause fatigue and reduced quality of life.

“This study is definitely not aimed at changing current practice,” said study author Dr. Peter Dubsky, of the Medical University of Vienna. “This is a retrospective analysis that has yielded quite controversial data. The conclusion from our study is aimed at experimental and clinical oncologic research. Anemia is associated with a high likelihood of tumor hypoxia [too little oxygen in the blood].”

The chemotherapy used in the study was a combination of cyclophosphamide, methotrexate and 5-fluorouracil (CMF). The problems of anemia and related local recurrence are probably not limited to just this form of chemotherapy, noted Dr. Douglas Yee, director of the University of Minnesota Cancer Center. “I think this effect would be seen with any chemotherapy.”

CMF is no longer commonly used in the treatment of breast cancer and has been replaced by other forms of chemotherapy such as taxanes, added Dr. Barry C. Lembersky, a clinical associate professor of medicine at the University of Pittsburgh School of Medicine. Also, there is a trend in breast cancer treatment to use chemotherapy less often, he said.

“Nowadays, there is a more selective use of chemotherapy, which tends to be used when a tumor is not stimulated by estrogen, lymph nodes are involved, or the genetic/clinical profile is suited for chemotherapy,” he explained.

In the Austrian study, CMF therapy was used as an additional treatment in 424 patients who were premenopausal and who underwent surgery as their main treatment for early-stage breast cancer. All had estrogen receptor-positive malignancies. The findings were published in the April 1 issue of Clinical Cancer Research.

The surgery was either a breast-conserving lumpectomy, which required additional radiation, or a modified radical mastectomy, for which radiation was optional. The radiation was given in the middle of chemotherapy treatment process, which is now an outdated method, Yee noted. “We tend not to do this kind of sandwich technique anymore,” he explained.

After an average follow-up of 61 months, 39 local relapses occurred among the 424 women: 6.9 percent in patients without anemia and 19.5 percent in patients with anemia. The five-year rates of local relapse were 8.2 percent among patients without anemia and 19.6 percent among patients with anemia.

In addition to anemia, two other factors — an older age at diagnosis and positive lymph node status — significantly increased the risk of a local recurrence of breast cancer. According to an analysis of the range of factors examined in the study, patients with anemia had a 2.96-fold increased relative risk of a local recurrence.

Since the Austrian research was conducted, the treatment of anemia in breast cancer patients has become controversial, Lembersky noted.

“Erythropoietin-stimulating agents are indicated for use by the FDA [U.S. Food and Drug Administration] when red blood cell counts are too low,” he said. “However, there is now controversy about their use due to the possible increase in tumor growth in breast cancer.”

Dubsky agreed.

“I am sure you are aware of the recent pitfalls in the use of erythropoiesis-stimulating agents (ESAs),” he said. “Given this context, we should start discussing anemia more in the context of tumor hypoxia and look for targets that are distinct from erythropoiesis.”

More informationHere’s more on the treatment of early-stage breast cancer.

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SOURCES: Peter Dubsky, M.D., Department of Surgery, Medical University of Vienna, Austria; Douglas Yee, M.D., director, University of Minnesota Cancer Center, Minneapolis; Barry C. Lembersky, M.D., clinical associate professor, medicine, University of Pittsburgh School of Medicine; April 1, 2008, Clinical Cancer Research

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Janice and Rodney Dietert display herbal and fungal medicinal sources that show promise for addressing developmental immunotoxicity (DIT) and DIT-associated diseases. On the tray are: sang-hwang mushroom, Panax ginseng, echinacea, shiitake mushroom and astragalus. (Credit: Image provided by Cornell University)

ScienceDaily (May 3, 2007) — A Cornell researcher and his wife have conducted the first comprehensive review of later-life diseases that develop in people who were exposed to environmental toxins or drugs either in the womb or as infants. They have found that most of the diseases have two things in common: They involve an imbalanced immune system and exaggerated inflammatory reactions (at the cellular level).

In an invited, peer-reviewed article on developmental immunotoxicity (DIT), published in a recent issue of Current Medicinal Chemistry, Rodney Dietert, professor of immunotoxicology at Cornell’s College of Veterinary Medicine, and Janice Dietert of Performance Plus Consulting in Lansing, N.Y., found that almost all the chronic diseases that are associated with DIT share the same type of immunological damage.

The diseases linked to DIT include asthma, allergy, suppressed responses to vaccines, increased susceptibility to infections, childhood neurobehavioral conditions, autoimmunity, cancer, cerebral palsy, atherosclerosis, hypertension and male sterility.

Toxins that are known to cause developmental immune problems in fetuses and neonates, according to the Dieterts, include herbicides, pesticides, alcohol, heavy metals, maternal smoking, antibiotics, diesel exhaust, drugs of abuse and PCBs.

Antidotes to DIT, the researchers note, could come from a variety of sources, including herbal and fungal chemicals — from mushrooms to clover — which appear to have promise.

Two immune processes — T helper (Th) cell balances and dendritic cell maturation — are both compromised in ways that disrupt the regulation of inflammatory cell function, which leads to exaggerated inflammatory responses.

“Most therapeutic approaches have looked at specific disease outcomes from DIT, rather than focusing on the underlying immune dysfunction that creates the increased disease risk,” said Rodney Dietert, who also presented his findings March 28 at the annual Society of Toxicology meeting in Charlotte, N.C. “Instead, we looked at the common immune dysfunction that is related to a host of diseases.”

Knowing the most common immune dysfunction patterns from DIT allows researchers to consider more seriously those “medicinals with the capacity to restore inflammatory cell regulation, promote dendritic cell maturation and restore desirable Th balance that would be the most likely candidates to combat the problems resulting from DIT.”

Focusing on studies of herbal and fungal chemicals, the Dieterts scoured the literature and found that some of the chemicals appear to be particularly promising when taken at appropriate doses. These include: Astragalus; Echinacea (purple coneflower); sang-hwang shiitake, reishi, maitake and snake butter mushrooms, black seed, Asian ginseng, milk vetch root, wild yam, Sophoro root and Greek clover (all of these also go by various other names).

In their paper, the Dieterts also list a multitude of substances that have been found to have “an uncertain impact” on DIT as well as several found to exacerbate immune dysfunction (including marijuana).

“We hope that these findings of persistent immune dysfunction from gestational exposure will provide encouragement for additional research. Furthermore, that researchers will look at these categories of medicines that have the possibility of correcting inflammatory and immune balance problems resulting from DIT rather than focusing solely on individual disease symptoms,” Rodney Dietert said.

He noted that until recently toxin-testing guidelines predicted only risk in adults, but that the Environmental Protection Agency has announced it will issue new guidelines to take into account the increased immune sensitivity of fetuses and young children.

Adapted from materials provided by Cornell University

What it is and why it occurs

Red blood cells carry oxygen throughout your body. Anemia is when you have too few red blood cells to carry the oxygen your body needs. Your heart works harder when your body does not get enough oxygen. This can make it feel like your heart is pounding or beating very fast. Anemia can also make you feel short of breath, weak, dizzy, faint, or very tired.

Some types of chemotherapy cause anemia because they make it harder for bone marrow to produce new red blood cells.

Ways to manage

• Get plenty of rest. Try to sleep at least 8 hours each night. You might also want to take 1 to 2 short naps (1 hour or less) during the day.
• Limit your activities. This means doing only the activities that are most important to you. For example, you might go to work but not clean the house. Or you might order take-out food instead of cooking dinner.
• Accept help. When your family or friends offer to help, let them. They can help care for your children, pick up groceries, run errands, drive you to doctor’s visits, or do other chores you feel too tired to do.
• Eat a well-balanced diet. Choose a diet that contains all the calories and protein your body needs. Calories will help keep your weight up, and extra protein can help repair tissues that have been harmed by cancer treatment. Talk to your doctor, nurse, or dietitian about the diet that is right for you.

When you get up from lying down, sit for a minute before you stand. Stand up slowly. You may feel dizzy if you stand up too fast.

Your doctor or nurse will check your blood cell count throughout your chemotherapy. You may need a blood transfusion if your red blood cell count falls too low. Your doctor may also prescribe a medicine to boost (speed up) the growth of red blood cells or suggest that you take iron or other vitamins.

Call your doctor or nurse if:

• Your level of fatigue changes or you are not able to do your usual activities
• You feel dizzy or like you are going to faint
• You feel short of breath
• It feels like your heart is pounding or beating very fast