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.
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
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
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
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
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
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.
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