F GUIDOZZI DEPARTMENT OF OBSTETRICS AND GYNAECOLOGY FACULTY OF HEALTH SCIENCES UNIVERSITY OF WITWATERSRAND

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1 F GUIDOZZI DEPARTMENT OF OBSTETRICS AND GYNAECOLOGY FACULTY OF HEALTH SCIENCES UNIVERSITY OF WITWATERSRAND

2 INTRODUCTION The onset of the menopause is often a time when women take stock of their health and express concerns about the chance of becoming ill. Such concerns can encourage healthy modifications of lifestyle which will maintain or improve general health. Cancer prevention : To understand their potential risks for cancer To encourage proactive preventative strategies To support early consultation when abnormal symptoms present To utilize health resources especially to be screened Screening policies and management vary from one country to another depending on resources and health-care policy.

3 Cancer incidence increasing because of longer life expectancy globally Cancer is an important cause of death, not primary cause of mortality. CVS disease represents 35-40% of deaths in most developed countries whilst 20-25% of women will die from cancer Preventative strategies include PRIMARY (patient driven) SECONDARY (screening, others) TERTIARY (surgical) Awareness programs

4 Breast, lung and cervical cancers are the most common in women, followed by colorectal cancer, stomach, ovarian, endometrial Mortality from breast cancer represent 13.7% of the mortality from cancer in women globally Lung cancer 13% Colorectal cancer 9% Cervical cancer 8.2% Mortality from ovarian cancer (4.2%) and endometrial cancer (2.2%) is much less.

5 BREAST CANCER Breast cancer is as common in developed countries (49%) as in developing countries (51%) Predominantly in postmenopausal women (67%), although it occurs more frequently in postmenopausal women in developed countries (39%) than in developing countries (28%). In 2010, over 1.5 million new cases of breast cancer were reported and there were over deaths globally Incidence is changing due to screening and life style modifications, but has increased globally

6 BREAST CANCER 10% are associated with strong genetic susceptibility (1) BRCA1and BRCA2 gene mutations where there is about 60% lifetime risk for breast cancer by 70 years of age (2) Lynch Syndrome (3) Family history Multifactorial associated with increasing sociocultural and education levels

7 CERVICAL CANCER Cervical cancer is more frequent in developing countries, where 80% of cervical cancer cases occur In 2012, more than half a million new cases of cancer of the cervix were reported together with 280, 000 deaths due to the disease. Third most common cancer globally, although it is the most common in black South African females, second most common in coloured women brought about by lack of screening and diagnostic facilities IN SA majority of cases present with late stage disease when diagnosed and burden of avoidable suffering is considerable

8 LUNG CANCER 520,000 new cases annually in women Mortality rate is still very high, 428,000 deaths annually World-wide incidence decreasing because of decrease in smoking Smoking main risk, pollution is issue in some countries Increase in female non-smokers due to passive smoking Low incidence in SA having cultural and economic and social determinants, only 4% of female smokers are Black, c/w 40% among Colored, 27% among White and 13% among Indian/Asiatic

9 COLORECTAL CANCER Colorectal represents 10 % of all incident cancers in women globally The lifetime risk of colorectal cancer is about 5% and is significantly affected by lifestyle factors Fourth or fifth most common cancer in Africa 5-10% originate from families with genetic predispositions. Hereditary non-polyposis colorectal cancer, LYNCH Syndrome Autosomal dominant expression, characterized by early onset colorectal cancer and microsatellite instability Additional 40-60% lifetime risk of endometrial cancer and 10-12% lifetime risk of ovarian cancer

10 ENDOMETRIAL CANCER Less frequent than breast, lung and colorectal cancers although commonest in western world Eighth to tenth most common in Africa Attributable global death rates in 2010 was 59,000 In Africa incidence increases with age peaking 70 years Risk factors include obesity, diabetes, nulliparity, ET, PCOS Not screenable and every PMB episode must be investigated

11 OVARIAN CANCER Disease of aging women and highest incidence is in those countries with higher life expectancy, with lowest global incidence in Africa Global deaths in 2010 was about 161,000 Incidence has not changed significantly in the last 30 years Usual late presentation BRCA1 & 2 carriers have 40% and 12% lifetime risk c/w 1.4% Lynch syndrome OCP, BSO, salpingectomy at hysterectomy, hysterectomy, tubal ligation all will decrease risk for cancer to varying degrees

12 MODIFIABLE LIFE STYLE RISK FACTORS Deaths attributable to risk factors in 2010 world-wide Number of 95% intervals Risk factor deaths of uncertainty Smoking Second-hand smoke Alcohol High body mass index Dietary factors and physical inactivity

13 ROLE OF OBESITY Obesity and BMI have increased globally and in developing countries. Obesity is risk factor breast, colon, endometrial and ovarian cancers.. BREAST CANCER Positive correlation in post-menopausal women, inverse correlation in premenopausal women. Obesity is also a risk factor for having a more aggressive breast cancer and worse survival.

14 COLON CANCER OBESITY Overweight and obesity, low physical activity and type 2 diabetes are linked to insulin resistance and increased risk for colon cancers in all kinds of populations ENDOMETRIAL CANCER Endometrial cancer and sarcomas increased in obese women Obesity negatively affects mortality whereas physical activity improves OVARIAN CANCER Diet high in cholesterol is significant in etiology of ovarian cancer

15 ROLE OF NUTRITION AND ALCOHOL Breast cancer Increasing consumption of alcohol is associated with an increase in the risk of hormone-dependent breast cancer. Colorectal cancers Intake of alcohol and red and processed meat associated with an increased risk, stronger for colon than rectal cancer Lung cancer Increased risk with cured meat, deep-fried cooking and chili

16 EPIC study Red meat < 500g/week Processed meat < 3g/day Alcohol <10g/day Fruits and vegetables >400 g/day Dietary fiber >25 g/day Physical activity 2 h/week vigor act, or 30 min/day cycl/sport Normal body mass index BMI kg/m² Overall, 12.6% (95% CI %) of all cancers could have been prevented in the whole study population Estimated diet, nutrition, physical activity, normalization of BMI may lead to a reduction of all cancer by 26% (6-42%) in the UK, 24% (7-40) in the USA, 19% (3-31%) in Brazil and 20% (5-37%) in China.

17 FRENCH STUDY life style aspects and cancer risk Smoking, physical activity, fruit and vegetable consumption, alcohol consumption, BMI 65,000 women aged years Significant decrease in postmenopausal breast cancer and lung cancer 7% decrease in all-site cancer risk 7% decrease in breast cancer 47% decrease in lung cancer

18 HRT AS A RISK FACTOR BREAST CANCER WHI EPT was initially associated with a 26% increase in risk Further analysis using centrally adjudicated data and adjusted 95% CI showed that risk was not significantly increased (RR=1.24) Absolute increase in risks equates to 4 extra cases per 1000 users of EPT for 5 years and only seen in previous users E only did not increase breast cancer risk at 6.8 years follow up (RR=0.77), whilst at 11.8 years in fully compliant users there was significant risk reduction (RR=0.67) which persists after stopping use for up to 5.9 years later

19 HRT AS A RISK FACTER BREAST CANCER Exercise decreases breast cancer even in HRT users. HRT risk primarily seen in lean patients ENDOMETRIAL CANCER Estrogens alone increase endometrial cancer risk. Addition of progestogens decreases risk of endometrial cancer. E and P preparations significantly decrease risk

20 HRT AS A RISK FACTOR LUNG CANCER Non-significant increase in risk of non-small cell lung cancer Significant increase in risk of death from lung cancer in women receiving HRT but not in the women in the estrogen-only trial. COLORECTAL CANCER 44% decrease in risk in E and P users which persists for 5 years after stopping therapy. No impact by E only therapy OTHERS Null-effect on melanoma, non-melanoma, oesophageal cancer, a decrease in stomach cancer and an increase in gall bladder cancer.

21 SECONDARY PREVENTATIVE STRATEGIES SCREENING Breast cancer Breast cancer screening is mostly performed using mammograms, every 2 years from 50 to 74 years of age. In lower middle-resource countries, CBE from ages 40 to 60 years could reduce breast cancer mortality at substantially lower cost. BSE and CBE with mammogram remain gold standard for breast cancer screening. Should ideally be digital and not film mammography Breast density very important. Sensitivity decreases from 88% to 62% to 67% in women with extremely or moderately dense breast tissue respectively

22 CANADIAN TASK FORCE GUIDELINES 2011 Reduction in mortality is relatively small in women aged years Greater reduction in mortality in women years than year Harms of over diagnosis and unnecessary biopsy may be greater for younger than older women Frequency of 2-3 years is appropriate

23 INDICATIONS FOR MRI SCREENING OF BREAST BRCA1 and 2 gene mutation carriers First degree relatives with breast cancer especially if diagnosed < 40 If life-time risk is greater than 20-25% Extremely dense breast History of lobular ca in situ or biopsy with atypical hyperplasia Any other high risk patient with uncertainty on screening modalities Previous thoracic radiotherapy

24 Prevalence of Cervical Neoplasia (%) SCREENING FOR CERVICAL CANCER PREVALENCE OF SIL AND CERVICAL CANCER BY AGE 6.0% 5.0% 4.0% LSIL HSIL Cancer 3.0% 2.0% 1.0% 0.0% < Age (Years) *Study conducted in rural Costa Rica (N=9175) 1. Herrero R, Hildesheim A, Bratti C, et al. Population-based study of human papillomavirus infection and cervical neoplasia in rural Costa Rica. J Natl Cancer Inst. 2000;92: Adapted with permission from Oxford University Press.

25 PREVENTION OF CERVICAL CANCER Cervical smear, HPV screening, Co-testing or VIA National policy of 1 screen per 10 years from 30 years onwards For women who have never been screened and who are >50 years old then one smear is to be offered Three yearly in HIV positive women Will decrease cervical cancer in SA by about 65% From a South African perspective, cervical cytology every 3 years, HPV testing every 5 years ( best as co-testing) from 50 years and continue to years

26 AMERICAN COLLEGE OF GASTROENTEROLOGY GUIDELINES FOR COLORECTAL CANCER SCREENING 2008 (a)colonoscopy every 10 years from 50 years of age. (b)alternatives Flexible sigmoidoscopy every 5-10 years CT colonoscopy every 5 years Fecal immunochemical test for blood annually

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28 WOMEN AT HIGH RISK FOR ENDOMETRIAL CANCER Known HNPCC genetic mutation carrier status Substantial likelihood of being a mutation carrier (known in family) Absence of genetic testing results in families with a suspected autosomal dominant predisposition to colonic cancer Long term unopposed E only therapy Postmenopausal bleeding Thickened endometrium especially if typical profile

29 SECONDARY INTERVENTION CHEMO-PREVENTION TAMOXIFEN.Breast cancer Vitamin D...Colorectal cancer Bisphosphonates Breast cancer Metformin..Endometrial/breast cancer Aspirin Colorectal cancer COX2 inhibitors..colorectal cancer Retinoids..Head and neck tumours

30 TERTIARY INTERVENTIONS LLETZ BRCA 1 and BRCA2 gene mutation carriers Role of routine salpingo-oophorectomy and total abdominal hysterectomy, with or without bilateral mastectomy to decrease risk of ovarian cancer, fallopian tube cancer and breast cancer Breast cancers invariably E, P, and Her2 receptor negative and therefore Tamoxifen is not effective LYNCH syndrome Every woman with endometrial cancer must have colonoscopy and every woman treated for colorectal cancer should have endometrial surveillance. Endometrial biopsy.

31 WHEN SHOULD WOMEN CONSULT FOR SYMPTOMS? Abnormal vaginal bleeding, abdominal or pelvic pain, distension, abnormal vaginal discharge, hematuria, or rectal bleeding. Breast nipple discharge or palpation of a lump, induration of a localized zone of the breast, a skin abnormality on the area of the breasts or nipple retraction, peau d orange. Unusual cough, dyspnea, hemoptysis or thoracic pain Occurrence of venous thrombosis in women without a family history can reveal a cancer.

32 CONCLUSION Cancer incidence is increasing as a consequence of longer life expectancy in developed and developing countries. Breast, colorectal, lung, cervical, endometrial and ovarian cancer are where the gynaecologist is most likely to make a difference Prevention must incorporate primary, secondary and tertiary interventions Primary strategies mandate patient life styles modification Secondary interventions mandate that screening strategies after which individual management of premalignant lesions is available Triaging women according risk factors can minimize risk by instituting appropriate surgical or chemo-preventative strategies Education and awareness programs are crucial

33 PREVENTING CANCER IN POSTMENOPAUSAL WOMEN THANK YOU FOR YOUR ATTENTION

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41 Franco EL et al. Vaccine :

42 HPV VACCINATION Very effective primary preventative strategy Target group ideally should be before HPV infection Offer full protection against types 16 and 18, although through cross protection offer protection against other high risk types Coverage again is important Vaccinating young girls and screening women over 30 years at 70% coverage for both will provide up to 70% reduction of cervical cancer Can vaccinate middle aged women, upto 45 years for the Quadrivalent and 55 for the Bivalent

43 BARRIERS TO SCREENING IN DEVELOPING COUNTRIES 1) Competing health needs 2) Limited human and financial resources 3) Poorly developed healthcare services 4) Women are uninformed and disempowered 5) War and civil strife 6) Widespread poverty 7) Type of screening test

44 VIA VISUAL INSPECTION AFTER ACETIC ACID APPLICATION Naked eye inspection, after 1 2 minutes of 3 5% AA Well-defined acetowhite areas NEGATIVE Absence of acetowhite lesions, faint ill defined translucent lesions, nabothian cysts or acetowhite dots VILI VISUAL INSPECTION WITH LUGOL S IODINE Naked eye inspection, immediately after application. Mustard yellow areas. Health mature squamous epithelium = BLACK or DARK BROWN Abnormal squamous epithelium = MUSTARD YELLOW In developing country option may include VIA or VILI and see-and-treat strategy with cryotherapy Denny et al. JAMA. 2005; 294: , Gaffkin et al. Lancet 2003; 361:

45 SCREENING OPTIONS Cytology based screening HPV DNA testing Visual inspection methods VIA VILI Colposcopy

46 PREVENTING CANCER IN POSTMENOPAUSAL WOMEN In any single country, differences in genetics, health care, and socioeconomic disparities can lead to differences in the mortality rate for a given cancer. USA where African-American women have 7% lower incidence rate of cancers compared to White women while their overall cancer-related death rate is 17% higher. In South Africa significant disparity exists with view to cervical cancer.

47 PRIMARY PREVENTATIVE STRATEGIES Stop smoking Control weight Exercise (vigorous exercise for at least 2-3 h/week) <15g/day alcohol intake Diet rich in vegetables, fibers and fruits (five fruit and vegetables/day but only two fruits, maximum three), low intake of animal fat, and a low proportion of carbohydrates.

48 PREVENTION OF CANCER IN POSTMENOPAUSAL WOMEN Mortality to incidence ratio is higher in developing countries compared to high-income regions especially Sub Saharan Africa Must decrease social inequities and improve access to health care for low-income groups. Implementation of better screening, diagnostic and management modalities of premalignant disease and incorporate our knowledge with view to hereditary influence in etiology of cancer Awareness programs alert women of their risk factors, life style modifications, provide information with view to screening tests will reduce the burden of disease and improve the prognosis for tumors detected at an earlier stage.

49 CONTROVERSIES SURROUNDING ROUTINE MAMMOGRAPHY OF LOW/MEDIUM RISK WOMEN Does not decrease mortality significantly, 1-3/1000 women screened l Improved survival was not through mammography but to improved treatment strategies Leads to about 1-20% of over diagnosis of breast cancer. Cancer that would never become clinically apparent : lead to diagnosis and unnecessary treatment of breast cancer Leads to repeated mammography, invasive biopsy procedures and surgical interventions because of high rate of false positive assessments High cost/benefit ratio, increases anxiety

50 SCREENING FOR CERVICAL CANCER ASCP, ASC, ASCCP Women aged >65 years with evidence of adequate negative prior screening and no history of CIN2+ within the last 20 years should not be screened with any modality Adequate negative prior screening defined as 3 consecutive negative cytology results or 2 consecutive negative co-tests within 10 years with most recent test within last 5 years Once screening discontinued it should not be resumed for any reason, even if woman reports having a new sexual partner South African perspective, cervical smear frequency from 50 years every 3 years, HPV testing every 5 years ( co-testing best option)

51 ENDOMETRIAL CANCER 1 and 2 or more risk factors increase cancer risk by 8- and 18-fold respectively Assuming a 2.6% lifetime risk, abovementioned risk factors confer a lifetime risk of about 18% and 32% respectively Small % are hormone independent and are poorly differentiated Not screenable and every postmenopausal bleed needs investigation Component of Lynch type syndrome

52 ENDOMETRIAL AND OVARIAN CANCER SCREENING There are no reliable screening tools for Ovarian cancer Endometrial cancer Lung cancer

53 PERFORMANCE AND CHARACTERISTICS OF DIFFERENT SCREENING TESTS