Breast Cancer Strategy Group of INCTR

1. Breast Cancer Strategy Groupof INCTR Goals & Objectives A Progress Report

2. INCTR • Non-profit organization. • Goals: • Development of infrastructure in collaboration with physicians & scientists of host countries for cancer treatment and control. • To improve understanding of genetic and environmental factors that predispose people to various types of cancers and thus develop prevention strategies. • Collaboration between the developed and developing countries.

3. Cancer Care in Developing Countries • It is estimated that by 2020, 80-90% of all cancers will be in developing countries which have only 5% of the world resources. • By 2020 nine million (75%) of the worlds cancer deaths will be in developing countries. • Cancers which can often preventable with access to screening, immunizations and information e.g. liver, cervical cancers etc are on the rise. • Over 80% of cancers are incurable due to lack of screening, late diagnosis and poor public awareness. • Financial constraints, illiteracy and co-morbid conditions also contribute to this dismal picture.

4. Epidemiology of Research in Low and Middle Income Countries (LAMI) • Over 85% of the worlds population lives in the 153 countries (World Bank Criteria). • Research is needed to meet the enormous and unmet health needs of LAMI countries. • Scientific journals play an important role in production and dissemination of research. • The gap between these and high income countries is widening in terms of publications. • At present only a fraction of research published in widely accessible oncology journals is from or about these countries.

5. Objectives of Disease Specific Strategy Groups Strategy groups comprises of investigators from developing countries who are interested in developing projects relevant to the study of disease of interest. Projects undertaken may include: • Translational research. • Epidemiological studies. • Clinical studies. • Educational programs for public and professionals.

6. Breast Cancer Strategy Group Meeting ; First • Brussels, May 29th,2002. • Participants: 24. • Purpose: To identify potential collaborative projects relating to early detection and treatment of breast cancer in developing countries.

7. Issues/Needs for Early Detection of Breast Cancer in DC-First The following points were highlighted during ensuing discussions: • Need to assess the incidence and demographic data in countries where cancer registries are not available. • Role of mammography as a population based screening tool in developing countries? • Need for alternative detection programs e.g. mammography in high risk groups only. • Need to assess efficacy of breast self examination and clinical breast examination by a physician. • Need of professional education. • Need for public education.

8. Ideas/Proposals for Collaborative Activities Related to Early Detection of Breast Cancer in DC-First • Training courses on cancer registration: Dr. Joe Harford (NCI) proposed to serve as contact person. • Development of public awareness program-demonstration project. • Validation of physical examination as screening procedure.

9. Ideas/Proposals for Collaborative Activities Related to Treatment of Breast Cancer in Developing Countries-First • Inflammatory breast cancer is more prevalent in developing countries but is ill defined. More information is needed. • Protocol for locally advanced breast cancer/inflammatory breast cancer needs to be developed. • Study biological differences of breast cancer in developing and developed countries however logistics are a problem.

10. Breast Cancer Strategy Group Meeting Sub-Committee (Jan 2003) Second Objectives: • To make some progress on the projects of interest identified in the May 2002 meeting. • Develop a study to identify characteristics and risk factors for breast cancer relevant to developing countries. • Project related funding should also be a component of various projects. • Presentations were made by various members of the sub-committee on epidemiological and clinical data.

11. Breast Cancer Strategy Group Meeting Sub-Committee (Jan 2003)India • Incidence of BC is increasing. • Accounts for 10% of cancers. • Higher incidence in urban areas. • Crude incidence rate higher in high SES and literate women. • Muslims and Parsi’s have a higher incidence. • Early stage disease in <25% patients. • ER positive tumors occurred with same frequency in pre and post menopausal women. • Women belonging to high SES and literate presented with early disease. • In 2 distinct time periods(1960-1989 vs. 1990-1998) public education programs did not affect disease stage significantly.

12. Breast Cancer Strategy Group Meeting Sub-Committee (Jan 2003)Peru • Incidence of BC is increasing and has now surpassed cervical cancer. • Patients generally belong to lower SES. • Most frequently occurs between 35-60 years. • 36% present with Stage I and IIA BC, II B in (14%), III (33%) and IV in (16%). • Risk factors include family history of BC or any cancer and obesity (needs to be better defined). • Poor follow up.

13. Breast Cancer Strategy Group Meeting Sub-Committee (Jan 2003)Eygpt • Cases analyzed were between 1986-1993. • 27% of all cases were breast cancers. • 85% received both chemotherapy and radiation. • 45% patients were <45 years. • 54% had T2 disease and 33% had T3-4. • 83% had MRM and 16% BCS. • Women with smaller tumors, lower grade and LN negative fared better. • Inflammatory breast cancer accounted for 15% of all BC cases.

14. Breast Cancer Strategy Group Meeting Sub-Committee (Jan 2003)Pakistan • Breast cancer incidence the highest reported from Asia other than Israel. • Median age 45 years. • No identifiable risk factors known in 70% cases. • MRM is performed in more than 95% cases. • Advanced disease present in >60% cases. • Poor outcome noted in patients belonging to low SES and illiteracy. • RR of developing BC is 1.44 in women born of first cousin marriages. • Incidence of BRAC1&2 is 8.4% in breast cancer patients.

15. Breast Cancer Strategy Group Meeting Sub-Committee (Jan 2003) • Dr. Guy Leclerq was interested in working on a collaborative project on genetic profile of breast cancer in developing countries. • His work suggests that that the ER receptor in our countries has a protein truncation which affects the binding of estradiol /tam. • He is also working on the types of BRCA1&2 mutations in developing countries.

16. Breast Cancer Strategy Group Meeting Sub-Committee (Jan 2003)Conclusions • Incidence of BC rising. • Risk factors for rising incidence need to be identified. • Lack of public awareness. • Advanced disease common especially related to lower SES and literacy. • Treatment strategies for developing countries need to be identified.

17. Breast Cancer Strategy Group Meeting Sub-Committee (Jan 2003)Conclusions On professional knowledge: • Lack of knowledge of referring physicians results in inadequate staging and diagnosis. • Patients mismanaged prior to referral. • Professional education of surgeons especially at district level hospitals essential. • Post fellowship training and up to date standards of care must be maintained.

18. Breast Cancer Strategy Group Meeting Sub-Committee (Jan 2003)Decisions • Due two paucity of information o breast cancer and lack of published data on outcomes etc. it was necessary that a formal collaborative retrospective study of BC cases should be undertaken at participating institutes. • Data collection will include risk factors, clinico-pathologic features, treatments, outcomes. • Period 1993-1997.

19. Breast Cancer Strategy Group Meeting (May 2003) Third • Objectives: • To obtain further information from participants about their perspectives on breast cancer in their countries. • Further development of breast cancer survey. • Development of treatment protocol for locally advanced breast cancer. • Possibility of conducting molecular studies.

20. Breast Cancer Strategy Group Meeting (May 2003) Third • The designed retrospective survey was circulated and discussed. • Modifications were made to improve the quality of information. • A pilot of 250 surveys will be done in order to determine problems of missing data and problems related to completion of survey.

21. Breast Cancer Strategy Group Meeting (May 2003) Third • Two other important decisions were taken: • Development of treatment protocol for locally advanced breast cancer. • To examine the role of neo-adjuvant chemotherapy in LABC. • Interest was expressed in comparison of CMF to anthracycline based chemotherapy. • To study estrogen receptor molecular heterogeneity and genomic profile of BC patients in developing countries.

22. Breast Cancer Strategy Group Meeting Sub-Committee (Early Detection) (Oct 2003, Fourth) Egypt • This meeting was attended by also Dr. Richard Chamberlain and Dr Amr Soliman from MD Anderson. • Efforts were needed to make early diagnosis and appropriate referrals as majority (60%) patients presented late and had inadequate treatment. • Mammography as a screening modality is not feasible and emphasis on clinical breast exam and self examination had to made. • Major discussion was focused on knowledge, attitudes and practices (KAP) of primary care physicians about BC in developing countries.

23. Breast Cancer Strategy Group Meeting Sub-Committee (Oct 2003) Egypt-follow up • A pilot study was undertaken in Egypt,Pakistan and Tunisia. • To identify strengths and weakness in medical education and primary health care practices. • Develop an educational programs to improve referrals and early detection. • A questionnaire was designed to assess KAP of physicians about BC , diagnosis, management and risk factors. • Development of questionnaires, lectures, and pre- and post-testing (March-August 2004) to: • 260 physicians in Pakistan • 150 physicians in Egypt • 75 physicians in Tunisia. • Data analysis is in progress. ● We anticipate the increase in the overall score of the questionnaire after the delivery of presentations underlying the basics of IBC.

24. Breast Cancer Strategy Group Meeting Sub-Committee (Oct 2003) Egypt-Result The module in Pakistan was conducted in one urban and 2 semi-urban areas: • It was very well received. • Younger doctors more receptive. • Doctors in urban areas understood the concepts better. • Urban and young doctors working in academic institutes were more receptive to change in thinking.

25. Breast Cancer Strategy Group Meeting Sub-Committee (May 2004) Objectives: • Finalize the retrospective breast cancer survey and agree upon plans for initiation. • Treatment protocol for LABC. • Specific biologic studies that can be undertaken for patients with BC.

26. Breast Cancer Strategy Group Meeting Sub-Committee (May 2004) • The retrospective survey was sent to Susan Komen Foundation for funding. • We were unsuccessful in getting the grant due to: • Quality of retrospective nature of study and associated pitfalls. • What impact it will have on the reduction or early diagnosis in women from developing countries? • The accuracy of data and subsequent comparison. • I think there is an unconscious perceived bias against research from developing countries as reviewers do not understand the difficulties of carrying out research and also question the validity of data .

27. Editors/Reviewers/Researchers for Low & Middle Income (LAMI) Countries • Editors and reviewers should be familiar with research needs and research infrastructure in LAMI countries. • Encourage publications from LAMI countries. • Include editors and reviewers with a special interest and expertise in LAMI countries in editorial boards.

28. Breast Cancer Strategy Group Meeting Sub-Committee (May 2004) • The group considered that despite setback retrospective study should be considered. • It was important to demonstrate that high quality data can be collected from the developing world. • It was also hoped that by gathering data the proposal could be resubmitted either as prospective or retrospective study in future. • Alternative sources for funding should be explored. • The target date for completion will be 18 months from the start of study.

29. Breast Cancer Strategy Group Meeting Sub-Committee (May 2004) • Protocol for LABC was discussed and in principle agreed upon. • A randomized 3 arm study will be conducted comparing standard treatment arm with FAC and CMF with concurrent RT in experimental arms. • A draft protocol will be discussed in this strategy group meeting.

30. Breast Cancer Strategy Group Meeting Sub-Committee (May 2004) • Dr Leclerq and Dr. Lacroix again attended the meeting. • They described their work on ER and their variants. • They are also studying patterns of gene expression in breast cancer. • Various collaborative projects were discussed. • Issues discussed were: Shipping of samples outside the country of origin & costs involved. • He was willing to train doctors if they could get funding through ICRETT etc.

31. Breast Cancer Strategy Group Meeting Sub-Committee (May 2004) Future directions • Role in professional educational activities. • Development of guidelines for the management of breast cancer. • Early detection programs and public awareness campaigns. • INCTR has been invited to participate in two meetings in which it might be an opportunity for strategy group members to develop a program tailored to needs of professionals in developing countries. • Participants agreed that more time was needed to formulate their ideas about the content for a professional education program.