Breast cancer chemotherapy and cognitive impairment
Los Angeles, CA. The authors of this paper introduce their study by pointing out that cognitive complaints among women who have received chemotherapy as part of the primary treatment for breast cancer are appearing with “concerning frequency.” Of eight recently published studies involving breast cancer survivors undergoing cognitive performance assessment, half have found memory to be particularly affected. This study from the University of California at Los Angeles and the VA Healthcare System of Los Angeles used positron emission tomography to compare control subjects with women having received chemotherapy. Subjects were scanned while performing control and memory related tasks in order to evaluate cognition-related cerebral flood flow. Specific alterations in activity were found for the frontal cortex, cerebellum and basal ganglia in breast cancer survivors by this approach to functional neuroimaging 5-10 years after the subjects had completed chemotherapy.
Silverman, D. H. S. et al. Altered Frontocortical, Cerebellar and Basal Ganglia Activity in Adjuvant-treated Breast Cancer Survivors 5-10 years after Chemotherapy. Breast Cancer Research and Treatment, 2006. Published electronically ahead of print.

Dangers of radiation therapy for breast cancer
BETHESDA, MD. It is well known that radiation is implicated in the process of carcinogenesis. An increase of breast cancer has been linked to ionizing radiation used for treatment of non-malignant and malignant diseases and in addition, excess cancers were documented among atomic bomb survivors. Thus an interesting question involves what if any risk of new primary cancers might be due to the therapeutic use of radiation along with surgery for breast cancer. A very large study has been recently reported in a document from the National Cancer Institute (in press) which is based on a huge database known as Surveillance Epidemiology and End Results (SEER), which in the case of this study covered the period from 1973 to 2000 with follow-up on over 300,000 women. Increased cancer rates for women having had radiation as part of their initial treatment were calculated by comparing with rates observed for non-irradiated patients. For those surviving 5-10 years, risk of cancer of the esophagus was increased 3-fold, bone 6-fold, and soft tissue 3-fold. For angio-sarcoma the ratio of observed to expected cases was over 17 and there was a correlation between the side irradiated and the location of the soft tissue sarcomas. This same correlation was observed with lung cancer where the 10-year relative risk was about 1.5. These increased risks were in general consistent with those observed in smaller studies. The authors do not discuss the risk-benefit aspect issue raised by this study.
Curtis, R. E. et al. New Malignancies among Cancer Survivors: SEER Cancer Registries, 1973-2000. NCI Publication # 05-5302, Chapter 7. (Free download available—“Google” NIH Publication 05-5302, identify the document and click “PDF available”)

Breast cancer – The importance of a second opinion
ANN ARBOR, MI. Breast cancer can present a diagnostic challenge, especially regarding such issues as the extent and histological nature of the disease. This in turn impacts management recommendations. In many cases, the initial diagnosis will not originate at a multidisciplinary breast cancer clinic. This study reviewed the medical records of 149 consecutive (to avoid bias) patients referred to such a clinic over a 1-year period. The records were reviewed retrospectively for changes in radiologic, pathologic, surgical and medical interpretations and the effect of these alterations on recommended surgical management was examined. The review of imaging studies resulted in changes in interpretations in 45% of patients studied, and this resulted in changes in surgical management in 11% of patients. Pathological reinterpretation resulted in 9% of patients having changes made in recommended surgical management, and for 34% of the patients, changes in surgical management resulted only from the multidisciplinary discussion with the surgeons, medical oncologists and radiation oncologists. Six patients were actually downgraded to benign disease. In all, approximately half the patients had a change in management as the result of this second opinion from a multidisciplinary center and for 32% of the women, the changes were based not on a disagreement about the radiology or pathology findings but rather on a different view of what constitutes the standard of care.
Newman, E.A. et al. Changes in Surgical Management Resulting from Case Review at Breast Cancer Multidisciplinary Tumor Board. Cancer, 2006, Vol. 107, pp. 2364-51.

NEWSBRIEF - Olive oil helps combat breast cancer.
There is ample evidence that the diet consumed in Mediterranean countries helps protect women against breast cancer. Now Professor Javier Menendez and his team at Northwestern University in Chicago suggest that olive oil may be the main protector. Dr. Menendez found that oleic acid, the major fatty acid in olive oil, is highly effective in killing the Her2/neu protein, a major factor in the growth of breast cancer tumours. The oil is, as a matter of fact, just as effective as the anticancer drug Herceptin and, when combined with this drug, results in a reduction of 70% in Her2/neu levels (in test tube experiments). Dr. Menendez suggests that olive oil manufacturers should begin to list the total oleic acid content on their products so that consumers can select the best brand for cancer prevention.
New Scientist, January 15, 2005, p. 7

Mastectomy versus lumpectomy – No survival difference
WASHINGTON, DC. There are two major alternatives for the surgical treatment of breast cancer. One, mastectomy, involves removal of the entire involved breast while the other, breast conservation therapy (BCT), involves removing just the tumour (lumpectomy) and subsequent radiation therapy. If the lymph nodes in the armpits (axillary lymph nodes) are found to be affected they are usually removed as well.

Researchers at the National Cancer Institute undertook a study between 1979 and 1987 to evaluate the survival rate of women who had undergone mastectomy as compared to women who had been treated with BCT. The 237 study participants have now been followed up for a median of 18.4 years. The survival rate for mastectomy patients over this period was 58% versus 54% in the BCT group – a difference that was not statistically significant. The disease-free survival rate was 67% for the mastectomy group and 63% for the BCT group – again a difference that was not statistically significant. There was no statistically significant difference in the number of women who developed cancer in the previously unaffected breast (7 in the mastectomy group and 5 in the BCT group). There was also no difference in the number of women who developed cancer at sites other than the breast (10 in each group).

The researchers conclude that there are no statistically significant differences in the survival rate or in the incidence of the development of new cancers between women treated with mastectomy and those treated with breast conservation therapy.
Poggi, MM, et al. Eighteen-year results in the treatment of early breast carcinoma with mastectomy versus breast conservation therapy. Cancer, Vol. 98, August 15, 2003, pp. 697-702

Curcumin and chemotherapy
CHAPEL HILL, NORTH CAROLINA. There is growing evidence that curcumin, a component of the spice turmeric, may be effective in the prevention of breast, prostate, colon, and oral cancers. Extracts containing curcumin have been used in India for generations in the treatment of inflammation, skin wounds, liver and gallbladder disorders, and persistent coughs. It is estimated that the average dietary intake of curcumin in India and certain parts of Southeast Asia is 200 mg/day or more.
Curcumin is a highly effective scavenger of reactive oxygen species (ROS) and also inhibits the JNK (c- Jun NH2-terminal kinase) pathway. Both ROS and an activated JNK pathway are crucial elements in successful chemotherapy. Researchers at the University of North Carolina now report that curcumin may interfere with the action of several chemotherapy drugs used in the treatment of breast cancer. Culture experiments showed that curcumin inhibited the cancer cell destroying capability of several chemotherapy drugs (mechlorethamine, Adriamycin, and camptothecin) by as much as 70%. The results were confirmed in experiments with laboratory mice. It is believed that curcumin exhibits its effect through ROS scavenging and inhibition of the JNK pathway.
The researchers conclude that more research is urgently needed to establish whether breast cancer patients undergoing chemotherapy should be told to limit their intake of curcumin and turmeric extracts.
Somasundaram, S., et al. Dietary curcumin inhibits chemotherapy-induced apoptosis in models of human breast cancer. Cancer Research, Vol. 62, July 1, 2002, pp. 3868-75

Hot chemotherapy
Encasing chemotherapy drugs in liposomes (hydrated phospholipid globules) before injecting them is becoming increasingly popular as it encourages the drugs to enter only cancer cells and leave healthy ones alone. Researchers at the Duke Cancer Center in North Carolina have found that heating up the tumours with microwaves or hot water (in the case of breast cancer) while injecting the liposomes make them far more effective. In a trial involving 21 women with breast cancer the researchers found that a combination of heat and chemo drug/liposomes shrank or completely destroyed all 21 tumours involved. Other medical centers have had equally encouraging results and work is now underway to test the technique on prostate cancer.
New Scientist, May 25, 2002, p. 13

Tamoxifen and endometrial cancer
AMSTERDAM, THE NETHERLANDS. Tamoxifen therapy has long been used in the treatment of metastatic breast cancer and in the prevention of recurrence of breast cancer. It is known that tamoxifen increases the risk of developing endometrial cancer, but so far it has been assumed that this "side effect" was of relatively little importance. Now researchers at the Netherlands Cancer Institute question this assumption. Their study involved 299 women who had developed endometrial cancer subsequent to being diagnosed with breast cancer and 860 matched controls who had been diagnosed with breast cancer, but had not developed endometrial cancer.
The researchers found that 36.1 per cent of the women with endometrial cancer had used tamoxifen as compared to 28.5 per cent in the control group. This translates into a 50 per cent greater risk among tamoxifen users. The risk increased with duration of use and was almost seven times higher for women who had taken tamoxifen for at least five years when compared to the controls. The severity of the cancer and the presence of sarcomas were also much higher among long-term users. The three-year endometrial-cancer-specific survival was 76 per cent for long-term tamoxifen users versus 94 per cent for non-users. The researchers calculate that 20 excess cases of endometrial cancer would develop in 1000 tamoxifen users followed up for 10 years. They conclude that the benefits of tamoxifen therapy still outweigh the risks in the treatment of metastatic breast cancer and in prevention of contralateral cancer. However, they seriously question widespread use of tamoxifen as a preventive agent against breast cancer in healthy women.
Bergman, Liesbeth, et al. Risk and prognosis of endometrial cancer after tamoxifen for breast cancer. The Lancet, Vol. 356, September 9, 2000, pp. 881-87
Gelmon, Karen. One step forward or one step back with tamoxifen? The Lancet, Vol. 356, September 9, 2000, pp. 868-69 (commentary)

Breast cancer surgery revisited
AMSTERDAM, THE NETHERLANDS. Breast conserving therapy (lumpectomy followed by radiation) has been shown to be as effective as mastectomy (removal of entire breast) in the treatment of breast tumors with a diameter of 2 cm or less. A team of medical researchers from Belgium, the Netherlands, South Africa, and the UK now report that breast conserving therapy (BCT) results in similar survival rates as mastectomy when dealing with larger tumors (2.1-5 cm) as well. Their study involved 868 women with stage II breast cancer who were randomly assigned to receive either BCT or radical mastectomy. After 10 years of follow-up there was no significant difference in the rate of survival among the BCT patients (65 per cent) and the mastectomy patients (66 per cent). The incidence of distant metastasis was also similar in the two groups over the 10-year follow-up period; 39 per cent for the BCT patients and 34 per cent of the mastectomy patients. There was, however, a significant difference in the recurrence of local tumors among the two groups. Among the BCT patients six per cent had a recurrence as compared to only 3.3 per cent in the mastectomy group. The 13-year survival rates were 60 per cent in the mastectomy group and 55 per cent in the BCT group. The researchers conclude that BCT and radical mastectomy result in similar survival rates among patients with stage II breast cancer.
van Dongen, Joop A., et al. Long-term results of a randomized trial comparing breast-conserving therapy with mastectomy: European Organization for Research and Treatment of Cancer 10801 trial. Journal of the National Cancer Institute, Vol. 92, July 19, 2000, pp. 1143-50

Tamoxifen may induce asthma attacks
DUNDEE, UNITED KINGDOM. Doctors at the Kings Cross Hospital warn that asthmatic women being treated for breast cancer with tamoxifen may aggravate their asthma. They describe the case of a 53-year old woman who had suffered from asthma for over 20 years. She was able to control her attacks with salbutamol. In 1990 she underwent surgery for breast cancer and was started on tamoxifen. Her asthma control subsequently deteriorated particularly a few hours after taking the tamoxifen. The doctors caution against prescribing tamoxifen to asthma sufferers without adequate precautions.
Smith, R.P., et al. Tamoxifen-induced asthma. The Lancet, Vol. 341, March 20, 1993, p. 772

Tamoxifen increases the risk of endometrial cancer
AMSTERDAM, NETHERLANDS. Researchers at the Dutch Cancer Institute have concluded that women who are given tamoxifen as part of their breast cancer therapy have a slightly increased risk (1.3 fold) of developing cancer of the endometrium. The risk increases markedly with the duration of the treatment; thus breast cancer patients who received 30 or 40 mg per day of tamoxifen for more than two years were found to have a 2.3 fold greater risk of developing endometrial cancer than did patients who had never received tamoxifen. The study involved a total of 383 breast cancer patients, 98 of which had developed endometrial cancer at least three months after the diagnosis of primary breast cancer. The researchers emphasize that the benefits of using tamoxifen in breast cancer therapy clearly outweighs the risk of developing endometrial cancer. However, they do question the wisdom of prescribing tamoxifen to healthy women in order to possibly reduce their future risk of developing breast cancer.
van Leeuwen, Flora E., et al. Risk of endometrial cancer after tamoxifen treatment of breast cancer. The Lancet, Vol. 343, February 19, 1994, pp. 448-52

Tamoxifen trial halted
PITTSBURG, PENNSYLVANIA. The National Cancer Institute has suspended a large scale study aimed at determining if tamoxifen will prevent breast cancer in women at special risk. The study which was started in 1992 was to involve 16,000 healthy women. Half would be given tamoxifen for five years, the other half, a placebo. All participants would be followed for seven years. The Cancer Institute halted the study when it found out that its leader, a renowned surgeon and cancer researcher, had been involved in another trial in which data had been falsified and suppressed. The falsified data occurred in a smaller trial of tamoxifen involving about 3,000 women with breast cancer. The researchers found that the rate of fatal endometrial cancer was much higher among the women taking tamoxifen than in the general population. They delayed the publication of the data and continued to sign up people for the large scale trial on healthy women without informing them of the danger. A congressional hearing is now underway to determine if the tamoxifen study should be permanently cancelled.
Marshall, Eliot. Tamoxifen: Hanging in the balance. Science, Vol. 264, June 10, 1994, pp. 1524-27

Breast-sparing surgery is as effective as mastectomy
BETHESDA, MARYLAND. The National Cancer Institute has just released a major study comparing the survival rates of breast cancer patients who had been treated with breast-sparing surgery (lumpectomy) and patients who had had a full mastectomy (removal of entire breast, lymph nodes in the armpit and part of the upper chest muscle). The researchers studied the outcome of almost 4,000 cancer operations and found that the survival rate amongst women who had undergone breast-sparing surgery followed by radiation treatment was equivalent to the survival rate of women who had had a full mastectomy. The researchers conclude that "Breast conservation treatment is an appropriate method of primary therapy for the majority of women with stage I and II breast cancer and is preferable because it provides survival equivalent to total mastectomy and axillary dissection while preserving the breast."
Abrams, Jeffrey, et al. Survival after breast-sparing surgery versus mastectomy. Journal of the National Cancer Institute, Vol. 86, No. 22, November 16, 1994, pp. 1672-73

Timing of breast cancer surgery is important
MILAN, ITALY. Scientists at the Italian National Cancer Institute have confirmed that the timing of breast cancer surgery in relation to the menstrual cycle is an important factor in preventing relapse. The researchers studied 1175 premenopausal women who had been diagnosed with breast cancer involving the axillary (armpit) lymph nodes. They found that 36.6 per cent of the women who had their surgery in the first half of their menstrual cycle (days 0-14) had a recurrence of their disease within five years. The recurrence rate was particularly high if surgery was performed immediately before ovulation (days 12-14). In contrast, women who had surgery during the latter phase of their menstrual cycle had a relapse rate of only 29.6 per cent. The researchers recommend that breast cancer surgery on premenopausal women be performed in the latter part of the cycle when axillary lymph node removal is involved.
Veronesi, Umberto, et al. Effect of menstrual phase on surgical treatment of breast cancer. The Lancet, Vol. 343, June 18, 1994, pp. 1545-47
Fentiman, Ian S., et al. Effect of menstrual phase on surgical treatment of breast cancer (letters to the editor). The Lancet, Vol. 344, August 6, 1994, pp. 402-04

Alpha-linolenic acid prevents breast cancer from spreading
TOURS, FRANCE. Medical doctors at the University Hospital in Tours have discovered that breast cancer victims who have a high content of alpha- linolenic acid (9,12,15-octadecatrienoic acid) in their breast tissue are less likely to develop metastases (cancer in distant organs such as the stomach, intestines, etc.). The study involved 121 women who had been diagnosed with localised breast cancer. The researchers analyzed samples of adipose (fatty) tissue taken close to the tumor at the time of surgery. They found that the cancer was more likely to have spread to the lymph nodes in the armpits in women with a low level of alpha-linolenic acid in their tissue. They found no relationship between alpha-linolenic acid content and tumor size. After an average follow up of 31 months, 21 of the women developed metastases. The researchers discovered that women who had a high adipose tissue content of alpha-linolenic acid at the time of surgery were five times less likely to have developed metastases than did women with a low content (less than 0.38 per cent). Original tumor size was also an important factor in predicting risk of metastasis which is the main cause of death among breast cancer patients. Women who had a tumor with a diameter greater than 5 cm had a 4.7 times greater risk of developing metastases than did women with smaller tumors. The researchers conclude that dietary supplementation with alpha-linolenic acid might delay or prevent the development of metastases in breast cancer patients. They also point out that previous research has shown that a high intake of dietary fat originating from fish helps prevent breast cancer in the first place and also improves survival among breast cancer patients. NOTE: Flax oil, pumpkin oil and purslane are good sources of alpha-linolenic acid.
Bougnoux, P., et al. Alpha-linolenic acid content of adipose breast tissue: a host determinant of the risk of early metastasis in breast cancer. British Journal of Cancer, Vol. 70, No. 2, August 1994, pp. 330-34

Mind-body connection gains acceptance
BETHESDA, MARYLAND. The effects of relaxation therapy and visualization on the immune system were the subject of a recent symposium sponsored by the National Institutes of Health. Dr. Mary Banks Jasnoski of the George Washington University reported that relaxing and imagining a powerful immune system can actually increase T-cell levels in people who are able to concentrate intently and who respond intensively to experiences and imagination. Dr. David Spiegel of Stanford University reported that women with metastatic breast cancer who participated in group therapy as part of their treatment survived twice as long as women who received medical treatment but no group therapy. Dr. Fawzy Fawzy of the University of California reported on a study he had done to evaluate the effect of psychological treatment on melanoma patients. The patients who all had had surgery for stage I melanoma were split into two groups. One group had a weekly 90-minute session of psychological treatment while the other group received no psychological support. The patients in the treatment group had half the rate of recurrence as the control group and about a third fewer deaths over five to six years. Work is now going on at Temple University to determine what psychological, social, and neuroendocrine factors are responsible in the development or avoidance of cervical cancer.
Flach, Jennifer and Seachrist, Lisa. Mind-body meld may boost immunity. Journal of the National Cancer Institute, Vol. 86, No. 4, February 16, 1994, pp. 256-58

Estrogen therapy may promote metastatic breast cancer
ROCHESTER, MINNESOTA. The administration of estrogen in low doses is believed to stimulate the growth of breast cancer cells. For this reason most doctors do not recommend estrogen replacement therapy for women with a history of breast cancer. Researchers at the Mayo Clinic now report that withdrawal of estrogen replacement therapy in postmenopausal women with metastatic breast cancer can lead to a regression of the cancer. Their study involved four postmenopausal women, three of whom had previously been diagnosed with breast cancer and operated upon. All four women were on estrogen replacement therapy to alleviate menopausal symptoms when they developed cancer in the bones or lungs. The reseachers stopped the estrogen therapy when the metastatic cancers were discovered and the cancers then regressed to the point where they almost disappeared; the improvement lasted for two to three years. The researchers recommend that estrogen withdrawal be the first treatment option for women who develop metastatic breast cancer while on estrogen replacement therapy.
Dhodapkar, Madhav V., et al. Estrogen replacement therapy withdrawal and regression of metastatic breast cancer. Cancer, Vol. 75, No. 1, January 1, 1995, pp. 43-46

Acceptance of lumpectomy growing
BETHESDA, MARYLAND. Radical mastectomy (removal of entire breast and lymph nodes) has long been the method perferred by surgeons in the treatment of breast cancer. This is now changing. Between 1983 and 1991 the use of lumpectomy (removal of tumor only) in breast cancer surgery rose from 16 per cent to 37 per cent while the use of radical mastectomy decreased from 75 per cent to 58 per cent. The preferential use of lumpectomy in in situ and in stage I cancers has grown even more pronounced. More than 50 per cent of all in situ cancers and slightly less than 50 per cent of all stage I cancers were treated with lumpectomy in 1991.
Ries, Lynn. Use of lumpectomy for breast cancer. Journal of the National Cancer Institute, Vol. 87, No. 5, March 1, 1995, p. 339

Melatonin blocks the growth of breast cancer cells
TUCSON, ARIZONA. A team of American and French researchers report some exciting developments concerning the ability of melatonin to retard the growth of breast cancer. Melatonin has previously been found to block the tumor-promoting effects of the hormone estradiol. Now it appears that melatonin also inhibits the tumor-promoter prolactin. The researchers carried out an experiment using human breast cancer cells grown in vitro. Human prolactin was found to increase the growth of the cancer cells by a factor of two. Melatonin completely inhibited the effects of prolactin although it had no effect on the growth rate of the cancer in the absence of prolactin. The tumor-promoting effects of human growth hormone was also found to be inhibited by melatonin. It is of significant interest that the greatest benefit of melatonin was found at levels equal to those normally found in the blood during the night. Higher concentrations of melatonin proved completely ineffective in inhibiting the prolactin- stimulated tumor growth. The researchers speculate that the normal nighttime secretion of melatonin is part of a natural mechanism which suppresses the growth of breast cells including cancerous ones. (NOTE: A completely dark bedroom is required for optimum secretion of melatonin).
Lemus-Wilson, A., et al. Melatonin blocks the stimulatory effects of prolactin on human breast cancer cell growth in culture. British Journal of Cancer, Vol. 72, No. 6, December 1995, pp. 1435-40

Tamoxifen trial halted
BETHESDA, MARYLAND. The National Cancer Institute has advised physicians to limit tamoxifen use to a maximum of five years for women with node-negative (non-involvement of lymph glands), estrogen-receptive breast cancers who have had lumpectomy and radiation treatment or mastectomy. The announcement follows the termination in November 1995 of the National Surgical Adjuvant Breast and Bowel Project's study of long-term use of tamoxifen. The project concluded that there are no additional benefits for women taking the drug for more than five years.
NSABP halts B-14 trial: no benefit seen beyond 5 years of tamoxifen use. Journal of the National Cancer Institute, Vol. 87, No. 24, December 20, 1995, p. 1829

Breast cancer overdiagnosed and overtreated
SAN FRANCISCO, CALIFORNIA. Ductal carcinoma in situ (DCIS) of the breast is a fairly common non-invasive form of breast cancer. Most cases of DCIS are detected through the use of mammography. It is estimated that DCIS accounts for about 30 to 40 per cent of all mammographically detected breast cancers and constitutes about 12 per cent of all diagnosed breast cancers in the United States. Almost all cases of DCIS are treated with some form of disfiguring surgery - this despite the fact that it is unknown whether the detection and treatment of DCIS actually extend the lives of the patients. The number of detected and surgically treated DCISs has risen astronomically since the introduction of screening mammography. Between 1973 and 1983 the age-adjusted rate for DCIS rose by 53 per cent in the United States. Following the introduction of mammographic screening in 1983, the incidence of DCIS increased by 328 per cent in the period between 1983 and 1992. It is estimated that at least 200 per cent of this 328 per cent increase is due to the use of mammography. The increase in diagnosed DCIS has been particularly high in women under 50 years of age where the growth in annual incidence rate was about 4,000 per cent greater for the period 1983-1992 than for the period 1973-1983.

In 1992, about 44 per cent of all cases of DCIS were treated with mastectomy (removal of entire breast), 23 per cent were treated with lumpectomy (removal of affected area only) plus radiation, 30 per cent were treated with lumpectomy alone, and about 3 per cent were not surgically treated at all. Survival rates during the first one to nine years were generally 100 per cent irrespective of type of treatment. The use of mastectomy was found to vary widely by geographical area from 28.8 per cent in Connecticut to almost 60 per cent in New Mexico. The authors of the recent report from the University of California express serious concerns about the increasing number of DCIS cases being detected through screening mammography especially since almost all of these cases are treated with disfiguring surgery. The concern is particularly acute in the case of younger women (30 to 39 years of age) where 92 per cent of all cancers detected by mammography are classified as DCIS. The authors conclude that there is an urgent need to study the appropriateness of the various treatment options from mastectomy to watchful waiting.
Ernster, Virginia L., et al. Incidence of and treatment for ductal carcinoma in situ of the breast. Journal of the American Medical Association, Vol. 275, No. 12, March 27, 1996, pp. 913-18
Page, David L. and Jensen, Roy A. Ductal carcinoma in situ of the breast. Journal of the American Medical Association, Vol. 275, No. 12, March 27, 1996, pp. 948-49

Timing critical in breast cancer surgery
LONDON, ENGLAND. Recent research has shown that the timing of breast cancer surgery is critical. Women who have surgery during the latter part of their menstrual cycle have a significantly better survival rate than do women who undergo surgery early in the cycle. Patients who are operated upon during the first 3 to 12 days of the cycle have the poorest survival while patients who have surgery between days 18 and 20 have the best survival rate. Now researchers at Guy's Hospital have found that blood serum levels of progesterone is an excellent indicator of the optimum time for surgery. A study of 289 premenopausal women who underwent mastectomy or lumpectomy showed that women whose progesterone level was higher than 4 nanograms/mL had a 76 per cent better survival rate (up to 18 years of follow-up) than did women with a progesterone level of less than 4 nanograms/mL. (Note: Progesterone levels rise as the menstrual cycle progresses and are highest in the luteal phase). Operating when progesterone levels are high is particularly important in cases where the lymph nodes are involved in the cancer. Here the survival rate was twice as good for women who had surgery when their progesterone levels were greater than 4 nanograms/mL.
Mohr, P.E., et al. Serum progesterone and prognosis in operable breast cancer. British Journal of Cancer, Vol. 73, No. 12, June 1996, pp. 1552- 55

Vitamin E succinate kills breast cancer cells
FREDERICK, MARYLAND. Several fat-soluble vitamins, namely vitamins A, D, E and K, have been found to inhibit the growth of cancer tumors. Now researchers at the National Cancer Institute report that vitamin E succinate (d-alpha-tocopherol succinate) actually kills certain types of human breast cancer cells in vitro. Their experiment involved two breast cancer cell lines (MDA-MB-231 and SKBR-3) which do not respond to antiestrogen therapy. The researchers found that vitamin E succinate (VES) inhibited the growth of the two cell lines in a dose-dependent manner. At VES concentrations of 5, 10 and 20 micrograms/mL the number of MDA-MB-231 cells decreased by 24, 67 and 85 per cent respectively after 48 hours. Similar results were obtained for the SKBR-3 culture. The researchers conclude that VES induces apoptosis (programmed cell death) through activation of a specific cell surface protein (Fas) rather than through any antioxidant or prooxidant effect. The researchers conclude that vitamin E succinate may be of use in the treatment of aggressive human breast cancers.
Turley, Jennifer M., et al. Vitamin E succinate induces Fas-mediated apoptosis in estrogen receptor-negative human breast cancer cells. Cancer Research, Vol. 57, March 1, 1997, pp. 881-90

Melatonin needs glutathione to combat breast cancer
COOPERSTOWN, NEW YORK. Melatonin, a hormone secreted by the pineal gland, has been shown to inhibit the growth of human breast cancer cells in concentrations (1 nM) similar to those encountered during the night when melatonin production is at its peak. Now researchers at the Bassett Research Institute report that the oncostatic (cancer-cell killing) effect of melatonin depends on an adequate concentration of the body's natural antioxidant glutathione. The researchers treated samples of breast tumor cell lines in vitro with melatonin (1 nM) and found that the number of cancer cells in the melatonin-treated substrates declined by 51 per cent after five days in incubation when compared to the control samples. They also observed that the glutathione levels remained much higher in the melatonin-treated cells than in the control cells. Conversely, when glutathione synthesis was artificially inhibited melatonin treatment no longer retarded the growth of breast cancer cells. The researchers also found that glutathione levels in cancer cells fell dramatically as the cells multiplied. They conclude that glutathione is required in order to produce the oncostatic effect of melatonin.
Blask, David E., et al. Physiological melatonin inhibition of human breast cancer cell growth in vitro: Evidence for a glutathione-mediated pathway. Cancer Research, Vol. 57, May 15, 1997, pp. 1909-14

Stress and cancer progression
COLUMBUS, OHIO. A diagnosis of breast cancer and subsequent surgery are highly stressful events which can lead to chronic stress. Reseachers at the Ohio State University now report that chronic stress in breast cancer patients decreases the effectiveness of their immune system and may reduce the benefits of adjuvant treatments such as radiation and chemotherapy. The study involved 116 women with stage II or III breast cancer who had recently undergone surgery. Before starting on additional treatments the patients completed a questionnaire designed to evaluate their stress level. They also gave blood samples which were analyzed for natural killer (NK) and T- lymphocyte activity. The researchers found that women with higher stress levels had impaired immune function as indicated by lower NK cell lysis (ability to destroy cells), diminished response to recombinant interferon gamma, and decreased T-cell activity. They speculate that patients with impaired immune systems may be less able to resist progression of the cancer and metastatic spread. Three studies are now underway to determine whether stress reduction through support group intervention can indeed slow tumour growth and disease progression.
Andersen, Barbara L., et al. Stress and immune responses after surgical treatment for regional breast cancer. Journal of the National Cancer Institute, Vol. 90, January 7, 1998, pp. 30-36
Cohen, Sheldon and Rabin, Bruce S. Psychologic stress, immunity, and cancer. Journal of the National Cancer Institute, Vol. 90, January 7, 1998, pp. 3-4 (editorial)
McNeil, Caroline. Stress reduction: three trials test its impact on breast cancer progression. Journal of the National Cancer Institute, Vol. 90, January 7, 1998, pp. 12-14 (news)