Archives for November 2016

Nov
19
2016

New Breast Cancer Cure?

According to the popular press there is a new breast cancer cure. But we have to be careful with general statements like this. First of all, only 20% of breast cancers are HER2 positive. When the surgeon biopsies breast cancer, he sends the sample to the pathologist. Out of 100 samples, 20 come back with the finding that it is HER2 positive breast cancer.

Herceptin ® (trastuzumab), the first step of breast cancer cure

Trastuzumab is a monoclonal antibody that interferes with the HER2 receptor. Its main use is to treat HER2 positive breast cancers. But trastuzumab (brand name Herceptin ®) has serious side effects. In early HER2 positive breast cancer it can cause heart failure in 5.7–35.4% of patients, while it can cure breast cancer with a 35% cure rate of Her2-positive patients. It is significant to note that many of the studies used trastuzumab in combination with the chemotherapeutic agent anthracycline concomitantly. Anthracycline by itself has some cardio-toxic effect. Most of the studies that investigated heart toxicity of trastuzumab used this monoclonal antibody for 52 weeks. Newer studies show that as little as 9 weeks can be as effective in tumor cures, which reduces the risk of toxic effects on the heart to 2.2–2.3%.

Here is a link that shows visually what the effect of Herceptin ® may be on the HER2 surface marker in a woman with this type of breast cancer.

Lapatinib (Tykerb ® or Tyverb ®), the second step of breast cancer cure

Over-expression of oncogenic receptor tyrosine kinases inhibits the absorption of aging cancer cells, called apoptosis. These are proteins that normally function to remove dying cells at the end of their life span. In HER2 breast cancer these kinases are particularly common and are responsible for the cancer cell survival. Lapatinib is a dual tyrosine kinase inhibitor, which interrupts the HER2 and epidermal growth factor receptor (EGFR) pathways. In simpler terms, it removes dying cancer cells, so they cannot reactivate the cancer or allow cancer cells to survive.

A phase 3 clinical trial was done with Lapatinib and a chemotherapeutic agent, capecitabine (brand name Xeloda ®). With combination of  the two drugs there was a 51% reduction in the risk of the disease progression.

Herceptin ® and Lapatinib combined as new breast cancer cure

At the 10th European Breast Cancer Conference in Amsterdam professor Nigel Bundred reported about a trial involving 257 women with newly diagnosed, operable, HER2 positive disease. The researchers recruited these women between November 2010 and September 2015. The physicians took biopsies and the surgery followed within 2 weeks.

The trial had two parts: The physicians treated the first 130 women with trastuzumab (Herceptin ®) only, or lapatinib (Tyverb ®) only, for 11 days after diagnosis and before surgery. From other trials evidence became known that the combination of trastuzumab and lapatinib had better survival rates. The investigators decided to include a second part into their trial starting August 2013 with 127 women. Part of this trial was a combination treatment of trastuzumab and lapatinib.

Samples of tissue were taken from the original breast biopsies and then again two weeks later from the material of the breast surgery.

The pathologist examined the breast cells for a drop in the Ki67 protein, an indicator of cell proliferation. They also looked for an increase of apoptosis of 30% or more from the first date of the first biopsy. A “pathological complete response” was the term they used for a cure. When there was a partial cure, this was termed “minimal residual disease“. This meant that the tumor was less than 5 mm in diameter at the time of surgery. Women who had received the combination treatment had 11% pathological complete response (11% cure rate). 17% of the combination therapy group had minimal residual disease. There was no cure for those randomized to only trastuzumab and only 3% of that group had minimal residual disease.

New Breast Cancer Cure?

New Breast Cancer Cure?

Conclusion

Essentially this new research shows that two inhibitor drugs together are better than one or one in combination with conventional chemotherapy.

But we have to keep in mind that HER2 breast cancer includes only 20% of all types of breast cancer. When you hear that 11% of HER2 breast cancer was cured with the combination therapy in 11 days, it translates into only 2.2% of all types of breast cancer cured and only 3.4% of all breast cancer cases had minimal residual disease (tumor size less than 5 mm in diameter). This could be easily removed by surgery.

What everybody is excited about are the cures of 2.2% of all types of breast cancer (or 11% of HER2 breast cancer). This is a good start. But much more research is necessary to increase the number of cures. While we are seeing some progress for one group of breast cancer patients, it is not nearly sufficient to advertise this treatment as a “cure”.

For all breast cancers a more promising option is available. A study from Wayne State University, Detroit, Michigan has shown that cryoablation therapy for breast cancer without excision can give a much higher cure rate of 100% over a period of 1 ½ years. In this procedure the physician leaves the tumor in place. Cryotherapy (extreme local cold temperatures) kills the tumor cells. It gives a cosmetically superior result. The FDA accepted this alternative treatment protocol, but cancer experts are slow to accept it.

Nov
12
2016

Stress Drives Our Lives

Every year the American Psychological Association (APA) monitors the American public how stress drives our lives. This yearly report has been compiled since 2007. About 75% of the people questioned reported that they have experienced moderate to high stress over the past month.

Symptoms when stress drives our lives

What kind of symptoms can stress cause? It can cause sleep deprivation, anxiety, headaches and depression. But there can be more symptoms from any disease that stress may cause. The “Stress in America” report from February 2016 shows on page 5 that unhealthy life habits are used by low-income Americans to cope with stress. A bar graph shows that watching television or movies for more than 2 hours per day is common. Another way of coping is to surf the Internet more often, take more naps or sleep longer. Eating more, drinking alcoholic beverages and smoking more are other unhealthy ways to cope with stress.

As the stressed person gains extra weight and eventually becomes obese, there is a higher rate of diabetes that can develop with all of its complications.

Causes of stress in our lives

The “Stress in America” survey was based on 3,068 adults in the US who completed the survey during August 2015. 72% were stressed out about financial issues. 22% of these said that they were extremely stressed in the past month as a result of money concerns. Other common concerns were work, the economy, family responsibilities and concerns about personal health. Average stress levels among Americans decreased when compared to 2007. On a 10-point stress score respondents rated their stress at 4.9 in 2016 compared to 6.2 in 2007. But according to the American Psychological Association this is much higher than a stress rating of 3.7 considered to be a healthy level.

Stress affects people from all walks of life, workers, women, young adults, students and those with lower incomes.

“Stress is caused by the loss or threat of loss of the personal, social and material resources that are primary to us” Stevan Hobfoll, PhD, a clinical psychologist from Rush University Medical Center said. “So, threat to self, threat to self-esteem, threat to income, threat to employment and threat to our family or our health…” is what causes stress.

Stress drives our lives causing disease

When stress is too much for our system, we are starting to see pathology develop. “Stress is seldom the root cause of disease, but rather interacts with our genetics and our state of our bodies in ways that accelerate disease” professor Hobfoll says. The following are common diseases that can result from chronic stress.

Heart attacks and strokes

In a 2015 Lancet study 603,838 men and women who worked long hours were followed for a mean of about 8 years with respect to heart disease or strokes. All of the subjects were free of heart attacks and strokes when they entered into the study. There were a total of 13% more heart attacks in those who worked extra hours in comparison to those who worked 40 hours per week or less. With respect to strokes there were 33% more strokes in those who worked long hours. Researchers noted a dose-response curve for strokes in groups with various workloads. Compared to standard working hours there were 10% additional strokes for 41-48 working hours, 27% for 49-54 working hours and 33% for 55 or more working hours per week.

Stress drives our lives and causes substance abuse

In order to cope with stress many of us treat daily stress with alcohol. It makes you feel good subjectively, but it can raise your blood pressure causing heart attacks and strokes down the road. A low dose of alcohol may be healthy, but medium and high doses are detrimental to your health.

Next many people still smoke, although scientists have proven long time ago that it is bad for your health. It can cause heart attacks, various cancers and circulatory problems leading to leg amputations.

Overeating is another common problem. Comfort food relieves stress, but it puts on extra pounds. As you know it is easier to put weight on than get it off. Being overweight or being obese has its own problems: arthritis in the hips and knees makes walking more difficult. The metabolic syndrome sets in, which is a characteristic metabolic change causing diabetes, high blood pressure, heart attacks, strokes and certain cancers. The more weight you carry, the less likely you are to exercise. This deteriorates your health outlook.

Diabetes

Stress causes too much cortisol secretion from the adrenal glands. This raises blood sugar, and when chronic can cause diabetes. In addition unhealthy eating habits associated with stress can cause weight gain and high blood sugars leading to diabetes.

In a 2012 California study 148 adult Korean immigrants were examined. They all had elevated blood sugars confirming the diagnosis of type 2 diabetes. They had a  elevated waist/hip ratio.

A high percentage of the study subjects had risk factors for type 2 diabetes. This included being overweight or obese and having high blood glucose readings. 66% of them said that they were feeling stressed, 51% reported feeling anxious, 38% said they were feeling restless, 30% felt nervous and 3% said they were feeling hopeless.

An Australian long-term follow-up study computed risk factors for developing type 2 diabetes. Stress was a major contributor to diabetes.

A 30-day episode of any anxiety disorder had a 1.53-fold risk to cause diabetes. A depressive disorder had a 1.37-fold risk to cause diabetes and posttraumatic stress disorder had a risk of 1.42-fold to cause diabetes.

Infertility

Stress changes hormones in women causing ovulation problems and infertility. 1 in 8 couples in America have problems getting pregnant. Physicians identified stress as at least a contributing factor. But in men stress can also reduce sperm count and semen quality as this study describes.

Alzheimer’s disease

A 2010 study from Gothenburg University, Sweden examined 1462 woman aged 38-60 and followed them for 35 years.

Psychologists assessed the stress score in 1968,1974 and 1980. 161 females developed dementia (105 Alzheimer’s disease, 40 vascular dementia and 16 other dementias). The risk of dementia was higher in those women who had frequent/constant stress in the past. Women who had stress on one, two or three examinations suffered from higher dementia rates later in life. Researchers compared this to women did not have any significant stress. Specifically, dementia rates were 10% higher after one stressful episode, 73% higher after two stressful episodes and 151% higher after three stressful episodes.

Remedies for stress

Before you can attempt to remedy stress, you must first detect that you are under stress. You can recognize this when you have problems sleeping, you suffer from fatigue, when overeating or undereating is a problem, and if you feel depressed. Others may feel angry or are irritable. Some bad lifestyle habits may also make you aware that you are under stress. You may smoke or drink more in an attempt to manage stress. Some people abuse drugs.

Here are some suggestions how to remedy stress:

  1. Seek support from family, friends or religious organizations. If you engage in drugs or alcohol overuse or you feel suicidal, it is best to seek the advice from a psychiatrist or psychologist.
  2. Engage in regular exercise. This produces endorphins, the natural “feel-good” brain hormone. This reduces symptoms of depression and improves sleep quality.
  3. Do something that increases pleasure, such as having a meal with friends, starting a hobby or watching a good movie.
  4. Positive self-talk: avoid negative thoughts like “I can’t do this”. Instead say to yourself “I will do the best I can”. Psychologists have developed a technique where they teach patients how to turn negatives into positives. Psychologists call this therapy “cognitive therapy”. You may want to seek the advice of a psychologist to have a few cognitive therapy sessions.
  5. Daily relaxation: you may want to use self-hypnosis, tai-chi exercises or meditation to reduce your stress levels.
Stress Drives Our Lives

Stress Drives Our Lives

Conclusion

Stress is very common. Diverse diseases like heart attacks, strokes, diabetes and Alzheimer’s disease can all be caused by stress. It is important to minimize the impact of stress by seeking family support and support from friends. Engaging in regular exercise will release endorphins and make you feel better. Relaxation exercises and seeking counselling can all help you to manage stress. You cannot ignore or simply tolerate this force in your life. Stress is indeed there, but we can make a difference by managing it to avoid that stress manages us.

Nov
05
2016

Health Risks Of Night Shifts

One of the news stories in 2016 was about health risks of night shifts. The Bureau of Labor Statistics reported in 2000 that 15 million workers (16.8 % of the working population) were doing alternative shifts (night shift work mixed with daytime shifts). In 2016 they reported 14.8% were working alternate shifts. Among blacks, Asians and Latino Americans the percentage of working alternative shifts was higher, namely 20.8%, 15.7% and 16%, respectively.

Shift work is more common in certain industries, such as protective services like the police force, food services, health services and transportation.

Evidence of health risks of night shifts

1.There are several publications that showed evidence of health risks of night shift workers. Here is a random selection to illustrate the health risks of night shifts.A study from 2015 examined the sleep patterns of 315 shift nurses and health care workers in Iranian teaching hospitals. They found that 83.2% suffered from poor sleep and half of them had moderate to excessive sleepiness when they were awake.

2.This South Korean study examined 244 male workers, aged 20 to 39 in a manufacturing plant. Researchers compared blood tests from daytime workers to blood tests from night shift workers. They also obtained inflammatory markers like the C-reactive protein and leukocyte counts. Night shift workers had significantly higher values. The investigators concluded that shift workers have increased inflammatory markers. This is a sign of a higher risk of developing cardiovascular disease in the future.

Higher mortality and higher cancer risk in nighttime workers

3. A Swedish study found that white-collar shift workers had a 2.6-fold higher mortality over a control group of daytime white-collar workers.

4. Another study compared night workers in the age group of 45 to 54 with daytime workers and found a 1.47-fold higher mortality rate in the night shift workers.

5.In a study from China 25,377 participants were included in a study that investigated cancer risk in males with more than 20 years of night shift work. They had a 2.03-fold increased risk to develop cancer compared to males working day shifts. Women with night shift work in this study showed no effect with regard to cancer development.

BMI and estrogen levels higher in women nighttime workers

6.A Polish study examined hormones and the body mass index (BMI) among 263 women who worked night shifts and 269 women who worked day shifts. When night shift workers had worked more than 15 years at nights, their estrogen levels, particularly in postmenopausal women were elevated compared to the daytime workers who served as controls. The BMI was also increased in the nighttime workers.

Risk for chronic lymphocytic leukemia higher in nighttime workers

7.Chronic lymphocytic leukemia (CLL): a study in Spain showed that working for more than 20 years in rotating night shifts was associated with a 1.77-fold higher risk of developing CLL. The authors noted that melatonin levels in that group were much lower than in controls that worked only day shifts. Working in straight night shifts did not show higher risks of CLL compared to daytime workers.

8. In a Korean study from Seoul 100 female medical technologist who worked nighttime had their melatonin levels tested, which were compared to daytime workers.  They measured 1.84 pg/mL of melatonin for the nighttime workers compared to 4.04 pg/mL of melatonin in the daytime workers. The authors felt that this is proof that the diurnal hormone system has been disrupted. Altering the melatonin level also changes the circadian hormone rhythm.

Flatter cortisol curves at night in nighttime workers, also increased diabetes risk

9.A group of 168 female hospital employees doing rotating nightshift work in Southern Ontario hospitals were compared to 160 day workers. Cortisol production was assessed. Cortisol production in day workers and in shift workers on their day shift was similar. However, shift workers on their night shift had flatter cortisol curves and produced less cortisol. The authors felt that this disruption of cortisol production would explain why rotating night shift workers have a higher risk of cardiovascular diseases.

10.A Danish study with female nurses followed 28,731 nurses between 1993 and 2015. Researchers measured the incidence of diabetes in rotating nighttime nurses in comparison to the data from daytime nurses. Night shift workers had a risk between 1.58-fold to 1.99-fold when compared to daytime workers to develop diabetes. The risk for evening shift workers was less (between 1.29-fold and 1.59-fold).

Diurnal hormone rhythm behind health risks of night shifts

Your body has its own rules. It rewards you, if you sleep 7 to 8 hours during the night, but it will penalize you severely, if you turn it upside down. The reason is our built-in diurnal hormone rhythm. A peak of melatonin regulates sleep during the night. Melatonin is released by the pineal gland (on the base of the skull) when it gets dark outside. Daytime wakefulness regulates the release of the stress hormone cortisol from the adrenal glands. These two hormones inhibit each other, cortisol inhibits melatonin and melatonin inhibits cortisol. All the other hormones are also regulated according to the diurnal rhythm: testosterone is highest in the morning, human growth hormone is highest between midnight and 3 AM etc.

Adjustment of the diurnal hormone system

When you work daytime shifts, your diurnal hormone rhythm works just fine. But if you work nighttime shifts, your hormones have to adapt. This is very similar to traveling east or west where you cross several time zones. Your internal diurnal hormone system has to adjust to these changes. Typically it takes 1 day to adjust to a 1-hour time zone difference.

Rotating shift workers have the highest risk of getting sick

In people who work permanent night shifts, the hormone changes stay adjusted and there is no further switching. But most employers want to be “fair” to everybody, so they introduced the rotating night shifts. The publications above show that this is the worst thing you can do. It messes with your diurnal hormone rhythm, and some people never switch completely to the new hours worked. They don’t get enough daytime sleep because the kids are loud during the day etc. The rotating shift workers are running the highest risk of getting sick. The get cancer, diabetes, cardiovascular diseases, obesity, cancer, leukemia, and they have low levels of melatonin.

Health Risks Of Night Shifts

Health Risks Of Night Shifts

Conclusion

Shift workers working constant night shifts is less stressful than the more common rotating shift work. This is where you work night shifts for a period of time. Then the schedule switches to day shift, and you keep on rotating. The least health risks occur with regular daytime work. People exposed to rotating night shifts suffer from poor sleep. They have a higher risk of gaining weight, getting obese and acquiring diabetes in time. They are at a higher risk for heart attacks, strokes and cancer. All-cause mortality is about twofold higher than for workers who work day shifts.

The underlying problem seems to be a disturbance of the diurnal hormone rhythm. Normally this regulates our waking/sleeping rhythm and keeps us healthy. But with nighttime work melatonin production weakens, there is less cortisol production and hormone rejuvenation during rest periods suffers greatly. This weakens the immune system, allows cancer to develop and leads to chronic inflammation causing cardiovascular disease and diabetes. The remedy to prevent this from happening is to catch little naps whenever you can during the day. And, if at all possible, work daytime shifts permanently.