Pakistan Youth Think Tank: 2009

Breast Health for Dummies

Pakistani women have the highest incidences of breast cancer in Asia. Do we just have bad luck or is there more to it than that?

“Worldwide, more than one million new cases of female breast cancer are diagnosed each year. It is also the most common female cancer in both developing and developed

countries” (Bray, McCarron, Parkin; “Breast Cancer Research,” 2004, BioMed Central Ltd.). More than 90,000 of the 1 million global cases of breast cancer are from Pakistan, and half of that number from Punjab. About 10% of them were diagnosed, out of which 75% of them did not seek treatment and died within five years. (University of Health Sciences controller of examinations Dr Junaid S Khan, speaking on ‘Cosmetic Options in Breast Disease Management’ (Daily Times, October 28, 2007). That means there are only 2,250 women in Pakistan who are treated for breast cancer out of yearly 90,000 cases! Pakistani women get the disease at a far younger age than Western women, with larger lesions, and are more prone to metastatic cancers. “The predominant morphology is a higher rate of infiltrating ductal carcinoma” (“Detection,” Sohail & Alam, JCPSP 2007 Vol 17 (12) pp. 711-712).

The highest reported (and researched) rates in the world are among Achkenazi Jews, who have a genetic mutation that has been reproduced via inter-marriages within their race. Why is it that around 1 in 7 to 8 women in Pakistan get breast cancer during their lives, while it inflicts 1 in 20 women in India, a country that is similar in terms of women’s ages during childbirth, marriage, and socio-cultural landscape? Then again, we all know that marriage between first cousins is still a common practice here, whereas in India, Hindus only marry cousins when they are 6 times removed. Many of them also follow vegetarian menus rather than, say, feasting on nihari gosht and paye cooked in ghee.

Ignorance plays a big role in the too-late-to-be-effective diagnosis of breast cancer in Pakistan. Here, if you go for a routine mammogram/breast sonogram, people look at you strangely and even the receptionist asks you why you’re there and if you have cancer (I kid you not!). That’s the whole problem. There shouldn’t be something wrong when you go. It ought to be a normal part of one’s health schedule just like routine gynaecological and dental checkups. Internationally, women get annual pap smears and mammograms and no one bats an eyelid. Here, it’s culturally unheard of to get yourself checked unless you have a noticeably hard lump and are forced by family members to consult a doctor.

Breast cancers in Pakistan often go undetected for so long that the majority of people are already in their 3rd or 4th stages by the time they realize they have it: “Pakistan faces a high burden of breast cancer disease with late stage presentation being a common feature. It has been seen that more than half of the patients present in advanced stages (stages III and IV). Regular clinical breast examination and mammography of women according to the internationally accepted guidelines can result in down-staging of breast cancer of asymptomatic women. However, there are no national screening programs for breast cancer in Pakistan. In the Pakistani context, educating the women about the risks of breast cancer constitutes a first step towards early detection of breast cancer, so that women would be able to judge their risk and take relevant measures” (“Breast Cancer Risk Factors Among Nurses In Teaching Hospitals In Karachi,” Ahmed, Mahmud, Hatcher, Khan; 2006 Aga Khan University study).

Many harmful pesticides and herbicides banned in developed countries are sold in developing countries and are identified as human or animal carcinogens, found in water supplies as well as in air and dust in homes(please refer to “DDT” section below). Ever since I can remember (and this dates back to the eighties), Pakistani TV has been full of advertisements of ‘kissans’ using magical ‘uriya’ and the like, spurning organic manure for profit-reaping cheap pesticides. Harmful chemicals linger in crops even after they are washed and cooked and enter our bloodstreams. In the meantime, western countries have adopted organic farming. People pay higher prices for organic items and shop at whole food stores, it’s considered very fashionable to eat organic. At an International Training seminar on Organic Farming in Islamabad, Dr. Kausar Abdullah Malik, Member Planning Commission and Ex-Chairman Pakistan Agricultural Council stated that Pakistan imported five times more pesticides than normal to control cotton pests for increasing production, and this had an adverse affect on the cotton crop, reducing it considerably. He said that organic farming was a more environmentally responsible approach to produce high-quality food and fiber (APP report, April 28th, 2008). He also thinks that DDT should be continued here because it ends malaria and is perfectly “safe.”

Although our research is scanty and there are no official reports, various health agencies have estimated that over 40,000 women die of breast cancer each year in Pakistan.

I wonder how many women’s lives would have been saved if they had been diagnosed sooner.

I wonder how many women would have gotten cancer in the first place if we didn’t use so many harmful chemicals in pesticides and other substances.

I wonder if our children can be saved from future agony if the government were to ban harmful chemicals, many of which are already prohibited in most countries.

I wonder when gynecologists will start citing mammograms and breast sonograms as mandatory checkups for women in their 30s and upwards, instead of waiting until they are already stricken with the disease.

I wonder when, along with Polio and other awareness drives, breast self-testing will be explained to rural and urban women.

I hope it’s before we have the highest rates of breast cancer in the world.

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The following information is derived from:

“State of the Evidence 2008: The Connection Between Breast Cancer and the Environment” (Edited by Janet Gray, Ph.D., published by the Breast Cancer Fund at www.breastcancerfund.org).

This study unveils the various sources, which increase our chances of contracting breast cancer, most of which, unsurprisingly, pertain to Pakistan:

Hormones and Endocrine-Disrupting Compounds Linked to Breast Cancer: There is broad agreement that exposure over time to natural and synthetic estrogens in the body increases the risk of breast cancer. Hormone replacement therapy (HRT) and hormones in oral contraceptives and some other pharmaceuticals also increase the risk. In fact, steroidal estrogens (the natural chemical forms of estrogen) are classified as known human carcinogens.  Synthetic chemicals that mimic the actions of estrogens are known as xenoestrogens, and are one category of EDCs that increase the risk of breast cancer by interfering with normal hormone function. Evidence indicates that EDCs also may contribute to early puberty, which is itself a risk factor for breast cancer. These compounds are present in many pesticides, fuels, plastics, air pollution, detergents, industrial solvents, tobacco smoke, prescription drugs, food additives, metals and personal care products, including sunscreens.

Pesticides: Some pesticides and herbicides have been labeled as human or animal carcinogens and many are found in water supplies as well as in air and dust in homes. DDT and its metabolite DDE is found in the body fat of humans and animals, and in human breast milk and placenta. The triazine herbicides—atrazine, simazine and cyanazine—have all been shown to cause mammary cancer in rats. Through different mechanisms, three other pesticides— heptachlor, dieldrin and aldrin—have also been shown to increase estrogen levels and/or stimulate growth of breast cancer cells. Of particular concern is the health of agricultural workers and their families, and communities affected by pesticide drift. Biomonitoring studies of children of agricultural workers revealed that high levels of pesticides can be found in the children’s urine soon after application in the fields near their homes. DDT, atrazine, heptachlor, diedrin, etc. are brought to people via outdoor and indoor air pollution, dust in households, non-organic food, and occupational exposures. Harmful pesticides and chemicals that contribute towards breast cancer include:

· DDT/DDE was the first widely used synthetic pesticide for agricultural and anti-malaria use, and has far-reaching effects. Recent research results show that exposure to DDT in early childhood alone is associated with a fivefold increase in risk of developing breast cancer before the age of 50. Most animals, including humans, ingest DDT-contaminated foods and retain the chemical and its main metabolite, DDE. Significant concentrations of DDT and DDE are still found in the body fat of humans and animals, in human breast milk and in placenta. Epidemiological data are mixed regarding the effects of DDT/DDE on breast cancer risk.

· PHTHALATES are used in plastics to make them soft and flexible. They also have the effect of disrupting endocrines, thereby rendering them cancerous. They are found in soft plastic babies’ toys, nail-polish, perfume, moisturizers, flavorings, and solvents.

· DIOXINS Of all toxic chemicals, dioxins may be the most widespread. The body fat of every human being, including every newborn, contains dioxins. Dioxins are formed by the incineration of products containing PVC, PCBs and other chlorinated compounds; as well as from industrial processes that use chlorine, such as pulp and paper manufacturing; and from the combustion of diesel and gasoline. Dioxins break down very slowly; they accumulate in fat of wildlife and bioaccumulate across the food chain. Dioxins are known human carcinogens and endocrine (hormone) disruptors. People are exposed to dioxins primarily through consumption of animal products and human breast milk. Dioxin enters the food chain when vehicle exhaust or soot from incinerated chlorinated compounds falls on field crops later eaten by farm animals. It is then passed to humans through dairy and meat products.

· BISPHENOL A (BPA) is one of the most pervasive chemicals in modern life. Billions of pounds of BPA are produced globally. BPA is the building block of polycarbonate plastic and is also used in the manufacture of epoxy resins. Significant levels of BPA have been measured in ambient air, house dust and river and drinking water. BPA is commonly found in the lacquer lining of metal food cans and in some types of plastic food containers, including some baby bottles, water bottles, microwave ovenware and eating utensils. Because BPA is an unstable polymer and is also lipophilic (fat-seeking), it can leach into infant formula and other food products, especially when heated. Once in food, BPA can move quickly into people” including fetuses while still in the womb.

· ALKYLPHENOLS: Alkylphenols are industrial chemicals used in the production of detergents and other cleaning products, as anti-oxidants in products made from plastics and rubber, also found in personal care products, hair products, and spermicides. It is found in all samples of house air and house dust samples, and wastewater associated with domestic sewers and municipal landfills.

· POLYSYCLIC AROMATIC HYDROCARBONS (PAHs) are ubiquitous byproducts of combustion, from sources as varied as coal and coke-burners, diesel-fueled engines, grilled meats and cigarettes. PAH residues are often associated with suspended particulate matter in the air, and thus inhalation is a major source of PAH exposure. Like many other environmental chemicals that are associated with breast cancer risk, PAHs are lipophilic and are stored in the fat tissue of the breast and increase risk for breast cancer through a variety of mechanisms. The most common PAHS are weakly estrogenic (estrogen mimicking), due to interactions with the cellular estrogen receptor (ER). However, the major receptor-directed pathway is a different one, with PAHs associating with a protein called the aryl hydrocarbon receptor (AhR), initiating a series of cell changes that lead to altered cell signaling and ultimately to increases in DNA mutations. PAHs can also be directly genotoxic, meaning that the chemicals themselves or their breakdown products can directly interact with genes and cause damage to DNA.

Carcinogens Linked to Increased Breast Cancer Risk: Two hundred sixteen mammary carcinogens have been identified, and cause cancer by damaging mammary cell DNA or cellular processes. They include industrial solvents used in the manufacture of electronics, textiles and furniture; vinyl chloride from polyvinyl chloride (PVC) used in medical devices, food packaging, toys, water pipes and many other products; 1,3-butadiene, a byproduct of petroleum refining and vehicle exhaust; ethylene oxide, a cosmetic ingredient and surgical instrument sterilizer; and aromatic amines, byproducts of manufacturing plastics, pesticides, dyes and polyurethane foams, as well as high-temperature grilling of foods. These include:

· 1,3-BUTADIENE is an air pollutant created by internal combustion engines and petroleum refineries. It is also a chemical used in the manufacture and processing of synthetic rubber products and some fungicides. In addition, 1,3-butadiene is found in tobacco smoke. The EPA determined that 1,3-butadiene is carcinogenic to humans, with the main route of exposure being through inhalation. The National Toxicology Program classifies 1,3-butadiene as a known human carcinogen. Data from research on animals indicate that females may be more vulnerable to the carcinogenic effects of 1,3-butadiene, which is known to cause mammary and ovary tumors in female mice and rats. This pollutant produces even greater toxic effects in younger rodent populations.

· AROMATIC AMINES are a class of chemicals found in the plastic and chemical industries, as byproducts of the manufacturing of compounds such as polyurethane foams, dyes, pesticides, pharmaceuticals and semiconductors. They are also found in environmental pollution, such as diesel exhaust, combustion of wood chips and rubber, tobacco smoke and in grilled meats and fish. There are three types of aromatic amines: monocyclic, polycyclic and heterocyclic. In a project exploring aromatic amine levels in breast milk of healthy lactating women, three monocyclic amines, including o-toluidine, were identified. O-Toluidine is known to cause mammary tumors in rodents. These data demonstrate both that the mother’s mammary tissue is being exposed to environmental carcinogens during breastfeeding. Perhaps of greater concern is the concurrent exposure of her newborn child. Heterocyclic aromatic amines (HAAs) are formed, along with PAHs, when meats or fish are grilled or otherwise cooked at high temperatures. A recent questionnaire study found an association between higher lifetime consumption of grilled meats and fish and increased incidence of post-menopausal breast cancer. Studies of both milk and cells from the ducts of women’s breast revealed the presence of DNA adducts in association with HAAs. These DNA adducts are indicators of problems in DNA repair in cells, one of the early hallmarks of tumor development. Laboratory studies of HAAs in systems using cultured breast cancer cells demonstrate that these chemicals can mimic estrogen, and they also can have direct effects on cell division processes in ways that, if also found in in vivo studies with intact tissues, might enhance the development of tumors.

· BENZENE is one of the highest volume petrochemical solvents currently in production, and global production rates are expected to continue to grow over the next several years. Chemical industries estimate that more than 42 million metric tons (more than 105 billion pounds) of benzene will be produced globally by the year 2010. Exposures to benzene come from inhaling gasoline fumes, automobile exhaust and cigarette smoke (primary and secondary) and from industrial burning. Benzene presents a serious occupational hazard for people exposed through their work in chemical, rubber and shoe manufacturing, and oil and gasoline refining industries. Both the NTP and IARC have designated benzene as a known human carcinogen. Epidemiological studies of the effects of benzene on breast cancer risk are difficult to conduct, mainly because exposures to benzene occur in conjunction with exposures to other chemicals that are also released in combustion and manufacturing processes. Also, few of the occupational studies focusing on chemical and automotive industries have included women in substantial numbers to draw meaningful conclusions. In one study that did look at relevant occupations among female Chinese workers, the occupations in which elevated risks for breast cancer were found included scientific research workers, medical and public health workers, electrical and electronic engineers, teachers, librarians and accountants. In the same study, looking across professions, benzene exposure was associated with an elevated risk of breast cancer. The largest and most convincing study implicating benzene and associated chemicals comes from an occupational study looking at men who have been diagnosed with breast cancer. Men who had worked in professions that involved exposures to gasoline fumes and combustion had significantly increased rates of breast cancer. The effect was most pronounced among men who started at their jobs before the age of 40. Benzene administration to laboratory mice induces mammary tumors. These animals have more mutations of genes that are responsible for suppressing the development of tumors.

· ETHYLENE OXIDE is a fumigant used to sterilize surgical instruments and is also used in some cosmetics products. Ethylene oxide is classified as a known human carcinogen and one of 48 chemicals that the National Toxicology Program identifies as mammary carcinogens in animals. Scientists from the National Institute for Occupational Safety and Health (NIOSH) studied breast cancer incidence in 7,576 women exposed to ethylene oxide while working in commercial sterilization facilities. They found an increased incidence of breast cancer among these women in direct proportion to their cumulative exposure to ethylene oxide. Although there are contradictory data in the recent literature, several other reports support the finding that exposure to ethylene oxide is associated with increased risk for breast cancer in women. Studies in which human breast cells grown in vitro were exposed to low doses of ethylene oxide demonstrated that the chemical exposure resulted in a significant increase in damage to the cells’ DNA.

· INYL CHLORIDE: Manufacturers use polyvinyl chloride (PVC) extensively to produce food packaging, medical products, appliances, cars, toys, credit cards and rainwear. When PVC is made, vinyl chloride may be released into the air or wastewater. Vinyl chloride has also been found in the air near hazardous waste sites and landfills and in tobacco smoke. Vinyl chloride was one of the first chemicals designated as a known human carcinogen by the National Toxicology Program (NTP) and IARC. Vinyl chloride has also been linked to increased mortality from breast and liver cancer among workers involved in its manufacture. Animals exposed long-term to low levels of airborne vinyl chloride show an increased risk of mammary tumors.

Policy and Research Recommendations: Hormones in Meat and Milk: Modern food-production methods have introduced new environmental exposures to carcinogens and endocrine-disrupting compounds. Pesticides on crops, antibiotics in poultry and hormones in cattle, sheep and hogs expose consumers involuntarily to unsafe contaminants every day. Consumption of animal products may hold inherent risks because animal fat can retain pesticides and other environmental toxicants consumed by the animal and research suggests that some of these exposures may increase breast cancer risk.  Since its introduction in 1993, bovine growth hormone (rBGH/rBST) has proven controversial because of its potential carcinogenic effects. Several studies have shown an association between dairy consumption and breast cancer in pre-menopausal women. rBGH has been shown to raise insulin-like growth factor 1(IGF-1) levels in the body; which have, in turn, been associated with an increased risk of breast cancer. Another food additive of concern is zeranol, a growth promoter used in the beef industry that mimics the effects of natural estradiol in the body.

INTERVIEW:

Q & A with Dr. Natasha Anwar, Consultant Molecular Biologist at Shaukat Khanum Memorial Cancer Hospital in Lahore:

Q Why is breast cancer the highest in Asia among Pakistani women?

We are still not sure why. However, it is likely that certain environmental and genetic factors are contributing to the high incidence of this cancer.

Q Is there genetic testing available in Pakistan for hereditary breast cancer genes BRCA-1 and BRCA-2? Who are likely candidates? (e.g. when 2 or more of their family members have had breast cancer before menopause?)

Diagnostic testing for BRCA1/2 mutations is currently not available in Pakistan however a research project is underway at SKMCH & RC that is identifying BRCA-1 and 2 mutations in patients with hereditary breast cancer. If a patient has a very strong family history of breast or ovarian cancer they and other members of their family are offered testing. There are specific criteria set out for genetic susceptibility testing, and it is only offered to individuals with a high risk of developing breast and or ovarian cancer. A high risk patient/family includes more than one first degree relative (mother, sister, daughter) with breast or ovarian cancer, more than one second degree relative (aunt, grandmother, cousin) with breast or ovarian cancer, a diagnosis of breast or ovarian cancer in these relatives at a young age (50 or younger).

Q I've read that Breast Cancer among men exists but it's rare. Have any men with breast cancer been treated at SKMCH?

Yes, breast cancer in men is rare. Between Jan 01 2008 and Jan 31 2009 a total of 953 cases of breast of these 5 patients were men (data courtesy of the Clinical Cancer Registry and Data Management section SKMCH & RC).

Q From the above study by the Breast Cancer Fund and the chart below, which do you think are applicable for Pakistan?

They may all be applicable; we need to carry out more specific research in order to determine the risk factors that are contributing to the development of breast cancer in Pakistani women. Another aspect is also diet.

Q Was my conjecture about inter-marriages as being a possible reason for the high rate of breast cancer in Pakistan ludicrous or does it seem a possibility?

Not at all ludicrous, in fact this is something that researchers are investigating at the moment.

Q Have there been any breast cancer drives in Pakistan at all?

Yes, SKMCH & RC initiated a breast cancer awareness campaign on October 25th 2008, and the Pakistan Pink Ribbon National Breast Cancer Awareness Campaign has also been active in this regard.

Q What are the chances of survival for a women if her cancer is diagnosed at an early stage?

Current data suggests that if breast cancer is detected at an early stage, before it has spread beyond the breast, the five-year survival is about 98% to 100% in the US.

Q By 'survival,' do you mean 5 years or more?

Normally when we talk about survival we specify if it is a 5 year or 10 year survival analysis. This does not mean that these women will survive only 5 years or 10 years. Doctors measure the success rates for cancer treatment by seeing how women are doing 5 or 10 years after treatment.

Q Is the government or the private sector doing anything to help promote/fund Breast Cancer awareness, diagnosis, and treatment?

As you know, SKMCH & RC treats 70% of its cancer patients free of cost, they are treated as patients would be anywhere else in the world. We have skilled experienced medical staff and excellent facilities that enable us to provide the best possible care. Patients are treated according to international protocols using the same medicines and drugs being given to patients in Europe and the US. The majority of our patients are women with breast cancer, and we see plenty of patients with advanced stage disease. It is more difficult to treat women who come to us with advanced breast cancer. To try and increase awareness and also educate women about breast cancer we have also been conducting various awareness sessions in schools and colleges. Our Nursing Division holds regular breast self examination sessions at the Hospital and they have also visited various companies and institutes to conduct sessions for female employees. We have also initiated a pilot breast cancer screening project, which is being run in vicinity in Lahore Pakistan. This will hopefully help us diagnose any breast cancer cases earlier.

There is another NGO working on Breast Cancer Awareness by the name of Pakistan Pink Ribbon Breast Cancer Awareness Campaign.

Q Is there anything else you'd like to add that women and men ought to know?

Never ignore your symptoms, certain cancers are completely curable if detected early so please if you are concerned consult your doctor or visit the Hospital. It is important to be aware of the risk factors, signs and symptoms of developing cancer.

PLEASE PROMOTE AWARENESS AND SAVE LIVES!!!

This has been published in Bluechip magazine