Tag Archives: therapy

Light exposure at night induces resistance to therapy in breast cancer

Cancer, Uncategorized, , , , , , , , , , ,

The disruption of melatonin production during the night through light exposure reduces tumor latency and drives resistance to tamoxifen in a model of estrogen receptor positive alpha (ERa+) breast cancer.

http://commons.wikimedia.org/wiki/File:Luz_en_Movimiento.jpg
http://commons.wikimedia.org/wiki/File:Luz_en_Movimiento.jpg

Melatonin is an hormone mainly produced by the pineal gland in the brain and primarily regulates sleeping habits. Its production is light sensitive; therefore, it is produced only in complete darkness, and sleeping in synthetic lights can interfere with its production. Melatonin has also been involved in the regulation of reproduction, timing of ovulation, aging, immune function, and cancer1. In 2001 a study linked night shift rotation with a moderate increase in breast cancer risk2. Studies have shown that melatonin antagonizes the metabolism of linoleic acid, the most prevalent polyunsaturated fatty acid present in the Western diet that upregulates the expression of genes controlling ER expression, cell cycle, and growth.

A group led by Dr. Steven Hill at the Tulane University (Louisiana)3 investigated how disruption of melatonin production influences not only growth but also response to tamoxifen of ERa+ tumors implanted into rats (xenograft). They did two sets of experiments. In the first set they compared animals kept under normal conditions with animals kept under dim light exposure at night (dLEN); in the second set, they compared dLEN mice with dLEN mice supplemented with nighttime melatonin. They found that tumors implanted in the dLEN rats had a shorter latency and a 2.6-fold increase in the growth rate compared with the controls. These tumors were also totally resistant to tamoxifen, whereas the control animals responded to the therapy. The dLED tumors showed high levels of proliferative markers, increased metabolism, and low apoptosis. Strikingly, when the nighttime melatonin was supplemented in the dLEN mice, tumor growth latency was reduced and resistance to tamoxifen was reestablished, with reduction of metabolism, proliferation markers, and increase in apoptosis.

Many studies have shown that melatonin can affect tumor growth in different cancer models, but this is the first study involving melatonin in resistance to therapy. The resistance to tamoxifen is a big problem in the treatment of ER+ breast cancer; about 30% of patients show resistance, and the causes are not totally understood. Strikingly, this research indicates that melatonin disruption affects resistance to therapy, through a molecular mechanism that may involve ER phosphorylation. Several lifestyle habits can influence cancer risk, cancer development, and resistance to therapy—e.g. diet, smoking, exercise. In addition, this report indicates that even sleeping in the darkness might be more beneficial against cancer.

Sleep in the dark!

1Melatonin, sleep disturbance and cancer risk. Blask DE.Sleep Med Rev. 2009 Aug;13(4):257-64. doi: 10.1016/j.smrv.2008.07.007. Epub 2008 Dec 17. Review.

2Rotating night shifts and risk of breast cancer in women participating in the nurses’ health study.Schernhammer ES, Laden F, Speizer FE, Willett WC, Hunter DJ, Kawachi I, Colditz GA.J Natl Cancer Inst. 2001 Oct 17;93(20):1563-8.

3Circadian and melatonin disruption by exposure to light at night drives intrinsic resistance to tamoxifen therapy in breast cancer. Dauchy RT, Xiang S, Mao L, Brimer S, Wren MA, Yuan L, Anbalagan M, Hauch A, Frasch T, Rowan BG, Blask DE, Hill SM. Cancer Res. 2014 Aug 1;74(15):4099-110. doi: 10.1158/0008-5472.CAN-13-3156.

The frightening effect of the word “cancer”

Cancer, , , , , ,

Did you know that Ductal Carcinoma In Situ (DCIS), noninvasive breast cancer, breast lesion or abnormal cells have all the same meaning? A very recent study from a team of the University of California San Francisco (UCSF) describes the impact of complicated medical terminology on patient treatment preference.

september 2013Since medical terms may sometimes sound too complicated and cryptic, health care provider’s communication with their patients is critical for a full understanding of medical conditions, diagnosis and treatments. In the research letter published on JAMA Internal Medicine on August 26th, Ozanne M. et al.1 explored the effect of Ductal Carcinoma In Situ (DCIS) terminology on the choice of patient treatment.

DCIS is the most common type of non-invasive breast cancer, accounting for the 20-25% of newly diagnosed breast cancers in the United States. It is treated with mastectomy or lumpectomy, with or without radiation therapy, and with or without adjuvant hormonal therapy2. In some low-grade cases, the progression may occur in a very long time frame (5 to 40 years), with no relevant clinical significance during patient’s life. Therefore, in these cases a watchful waiting period has been proposed instead of a treatment, even if it might be difficult to convince of this a patient who has just discovered to have “cancer”.

The team of doctors from UCSF hypothesized that without using the word cancer, the women diagnosed with DCIS might be more prone to non-invasive approaches. They surveyed 394 healthy women with no history of breast cancer and presented them 3 scenarios to describe the diagnosis of DCIS: noninvasive breast cancer, breast lesion or abnormal cells. To all of them was presented the same outcomes and options of treatment (surgery, medication, or active surveillance). They found that when DCIS was described as a high risk condition (breast lesion, or abnormal cells) instead of a cancer, more that 66% of women chose non-surgical treatments, whereas when the term noninvasive cancer was used only 53% of the participants chose a non-surgical option.

As pointed out in the original article, the current study has some limitations, being performed on a restricted cohort of educated and well insured women, different from the cohort of DCIS patients, and without taking into account specific factors, such as tumor grade and age. Although this analysis was performed on healthy women who didn’t have cancer, it suggests that many patients may prefer noninvasive therapies, when allowed to carefully consider risks and treatments, pointing out the importance of the terminology used by health care providers.

Too often, people are confused after leaving their physician’s office and this is something that should not happen, especially when dealing with serious and heterogeneous diseases, such as cancer. Hopefully this study is not a drop in the bucket and will be taken into consideration in the future, leading to a careful elucidation of the puzzling medical dictionary.

1              Omer, Z. B., Hwang, E. S., Esserman, L. J., Howe, R. & Ozanne, E. M. Impact of Ductal Carcinoma In Situ Terminology on Patient Treatment Preferences. JAMA Intern Med, doi:10.1001/jamainternmed.2013.84051731962 [pii] (2013).

2              Virnig, B. A., Wang, S. Y., Shamilyan, T., Kane, R. L. & Tuttle, T. M. Ductal carcinoma in situ: risk factors and impact of screening. J Natl Cancer Inst Monogr 2010, 113-116, doi:10.1093/jncimonographs/lgq024lgq024 [pii] (2010).