Ann Fonfa San Antonio Breast Cancer Symposium 2001 By Ann Fonfa This year was the 24th Annual Symposium. Each year oncologists, surgeons, pathologists, advocates and some other healthcare professionals gather to listen to the latest studies and share information. The meeting lasted 4 days. The Alamo Breast Cancer Foundation offers scholarships to advocates to cover costs of attending (conference fee a mere $50.00). At the end of each day they hold a meeting of all the scholarship recipients, although all advocates are welcome to sit in. Various doctors answer questions from the advocates and help explain the information they heard that day. Each advocate is assigned a group of presentations they have to write a report on. These reports are bound into a soft-cover book, printed and distributed to the advocates. See their site below for more information. The first speaker was Fran Visco, Esq., head of the National Breast Cancer Coalition (NBCC) who spoke on "The Role of Breast Cancer Advocates in Setting and Advancing a Research Agenda". This was in great contrast to Ms. Visco's talk at the annual meeting of the American Association for Cancer Researchers where she is usually the final speaker on 'Public Day'. Since the presentations to researchers start at noon, there is usually an exiting of them from the auditorium. She complained at this year's meeting that she ought to come first. And here she was. She told the audience that more than $1 billion dollars have been raised since 1993 in new research dollars as a result of the advocacy community. She discussed the Department of Defense Breast Cancer Research Program which has involved advocates to an unprecedented degree. http://cdmrp.army.mil.bcrp She also discussed the Clinical Trials Project, established by NBCC which educates advocates and the public. Many advocates from around the country participated this year in an educational meeting. NBCC also runs Project LEAD which is a week long educational training on basic science which helps prepare advocates to participate in review boards. NBCC has collaborated with some companies to help recruitment for their clinical trials. Criteria includes reimbursement of patient costs, results to be made public regardless of outcome even if ended early or cancelled. Ms. Visco pointed out that only about 20% of medicine is based on rigorous research evidence. She finished her talk by stating that it is our job to challenge assumptions. The next talk was by Dr. Trevor Powles of the Royal Marsden National Health Service Trust. He spoke about "A randomised placebo controlled trial to evaluate the effect of the bisphosphonate, clodronate, on the incidence of metastases and mortality in patients with primary operable breast cancer". Bisphosphonates as a class of drugs were introduced in 1991, although work was begun thirty years ago. (Is anything really new?). The women in this study were very evenly matched in both arms. Similar ages, conditions, ER status etc. The results seemed to show an increase in survival in the clodronate arm. The effect of the drug ended when they ceased taking it. Therefore duration of medication is a critical issue. From their conclusion (in the abstract) "Adjuvant clodronate significantly reduces the incidence of bone metastasis during the medication period, associated with a significantly reduced mortality". Another issue, from my perspective, is the failure of any study to compare clodronate (Bonefos) with pamidronate (Aredia) or the newest, as-yet unapproved bisphosphonate, zolodronate (Zolodex) to each other. And yet, some advocates say that since these are "me too" drugs, maybe that is a waste of our precious resources. A good point. Europe and Canada have been using clodronate while the U.S. has favored pamidronate. Is there a difference? Is one better than the other? Could there be a financial motivation involved, as the U.S. drugs are infusions which tend to cost more? A talk by Dr. R.E. Smith on "Acute myeloid leukemia and myelodysplastic syndrome following doxorubicin-cyclophosphamide adjuvant therapy for operable breast cancer: the NSABP experience" discussed the higher risk of developing these two conditions following therapy. NSABP=National Surgical Breast & Bowel Project and is a governmental group that handles big trials and big issues. They ran the Breast Cancer Prevention Trial P1 on Tamoxifen versus Placebo and are involved in many other important studies. Several facts stood out: greater risk over the age of 50; greater risk with use of G-SCF dose (prophylactic support for febrile neutropenia); personal toxicity levels and radiation therapy. However, Dr. Smith pointed out that the risk of AML remains small compared to the relapse rate of 35% in five years. (Of course, from my perspective this demonstrates we do not have a good enough handle on treatment options). Conclusions from the abstract "Intensified doses of C requiring G-CSF support were associated with increased incidence of AML/MDS, although this increased risk was small relative to breast cancer relapse. In-breast radiotherapy also appeared to be associated with increased risk of AML/MDS." Dr. George Sledge spoke about "Pilot trial of paclitaxel (Taxol)-herceptin adjuvant therapy for early stage breast cancer (E2198)". There were almost 20% of patients with lowered left ventrical fractions and less than 2% with congestive heart disease. The long term effects are yet to be determined. Conclusions: "We conclude that trastuzumab (Herceptin) has rare but real cardiac effects in anthracyline-naive patients receiving adjuvant chemotherapy." I believe Dr. Dennis Slamon has spoken negatively about this combination. (Slamon is the original researcher on Herceptin). A presentation on the preliminary results from NSABP Protocol B-27 on neo-adjuvant chemotherapy (prior to surgery). This trial compared the addition of sequential Taxotere to Adriamycin (doxorubicin) and cyclophosphamide. At this point there is no correlation to improved overall survival (OS) or even disease-free survival( DFS). However more women are able to have a lumpectomy rather than mastectomy as surgical treatment. The big news at the conference was all about the aromatase inhibitors and the next study discussed "Serum HER-2/neu and response to the aromatase inhibitor letrozole versus tamoxifen", delivered by Dr. A. Lipton. Bottom line overall survival was 9.4 months on letrozole versus 6.2 months on tamoxifen. "This study confirms serum HER-2/neu as a negative predictive factor for response to endocrine therapy in this advanced breast cancer population". Dr. E. Tan-Chiu discussed "The effect of tamoxifen on benign breast disease. Findings from the National Surgical Breast and Bowel Project (NASBP) Breast Cancer Prevention Trial. She stated that estrogen receptors are expressed in benign breast disease. The least risky ones include duct ectasia, fibrosis, mild hyperplasia, cysts, adenosis, metaplasia and fibroadenomas. More problematic in terms of future disease is atypical ductal or lobular hyperplasia, DCIS. Between April 1992 and March 1998 with a median time of 54.6 months, women were studied. All the above diseases showed reduction in the tamoxifen arm. Women age 49 and younger experienced the strongest results. There were 1415 biopsies in the group taking tamoxifen versus 1804 for those on placebo. Conclusions: "Tamoxifen therapy reduced the incidence of diagnosed benign breast disease in the categories of adenosis, cysts, duct ectasia, fibrocystic disease, hyperplasia and metaplasia, but not the incidence of fibrosis or fibroadenoma. It also reduced the total number of biopsies". Dr. Michael Baum gave an important presentation on "The ATAC (Arimidex, Tamoxifen, Alone or in Combination) adjuvant breast cancer trial in post-menopausal women". This trial recruited 9336 women of whom about 20% had chemotherapy, 1/3 were node positive, 16% had negative ER or unknown status and some had been given tamoxifen prior to surgery. The important information from this trial showed that cognitive function and bone mineral density were strongly affected. Dr. Anthony Lucci, Baylor College of Medicine, discussed the fact that there were reimbursement issues with conservation surgery (lumpectomy) and SNB (sentinel node biopsy) which may make some doctors less likely to perform either. He showed that some doctors are performing SNB after only ten practice surgeries. This seems too few as the learning curve appears to be somewhere between 20 and 30. A mentor is usually recommended as well. He was concerned about new doctors who might not learn techniques for performing appropriate lymph node dissections. He also doubted than any non breast surgeon would have the experience needed. I believe that these practice sessions should include some patients that have larger tumors. Several reasons apply; 1) a large minority of these patients do not have lymph node involvement and they should have achance to find out 2) better to 'practice' on those who will NEED an axillary dissection than those who probably do NOT and 3) the experience will probably be useful. Dr. Lucci told the audience that about 13% of surgeons are performing SNB on patients with DCIS. He stated "there is NO role for the routine use of sentinel lymph node dissection with patients who have DCIS". If the DCIS is extensive and there is an invasive component, then SNB or low level dissection may be performed. With DCIS patients, micro-metastases can be identified retrospectively 6-13% of the time. One study showed that benign epithelial cells could be displaced into the lymph nodes after a biopsy. Of course this could happen with malignant cells as well. He said there was no data to support the routine removal of internal mammary nodes. He expressed concern that there was low minority enrollment in the SNLB studies and very few community-based hospitals involved. He suggested mentoring into these underserved communities. In a survey of Texas hospitals, only 5% had credentialing guidelines for SNB. The American Board of Surgery has recommended that residents get training. A presentation by Dr. D. Clarke from Cardiff, Wales, UK revealed that UK surgeons are only performing SNB as part of ongoing studies. They have found that "if surgeons are adequately trained and proctored in this new surgical technique, ...the failed localisation and false negative rate can be reduced to safely acceptable levels". Dr. Kristin Skinner discussed "Risk of invasive local recurrence following therapy for ductal carcinoma in situ is a function primarily of time". This was based on NSABP data. 16% of DCIS patients treated with breast-conserving surgery (lumpectomy) had local recurrence and 32% of all other patients treated with lumpectomies after almost 12 years of follow-up. As usually found, margin status was of primary importance (clean margins are critical in DCIS, less than 1 mm (12X higher risk compared to 1cm). 9mm of clear margin showed a 4X higher risk of recurrence. Tumor size was somewhat important but no factor stood out beyond margins as an association for invasive recurrence. 44% of recurrences were invasive and 12% non-invasive. There was nothing found that seemed to prospectively predict for invasive local recurrences, but there may have been missed information at diagnosis. The study found a .7% risk for cancer in the contralateral (opposite) breast. Dr. Jay Harris, Harvard Medical School spoke on "Prognosis following local recurrence after conservation surgery and radiation therapy for early-stage breast cancer". The ten year rate for local recurrence after lumpectomy and radiation therapy is put at 5-20%. Neither prognosis nor optimal treatment is well defined. This study looked at 2102 patients between 1970-1987. There were 318 local recurrences. 288 patients were further studies with a median age of 45. 27% had positive lymph nodes. 20% of the patients had received adjuvant systemic therapy. 58% of the patients had both nodal and breast radiation. The median time to local recurrence was 65 months (1-220 months). 11% had non-invasive recurrence. 59% of these women were alive at 10 years. Those with lobular carcinoma were 2.4X more likely to develop local failure or to die from the disease. This was a retrospective look at patients with the potential for misclassification. But mastectomy seemed to be more effective in patients who had local recurrence. Conclusions:"Patients with local recurrence after (lumpectomy) and radiation can have prolonged disease-free survival, particularly when treated with a mastectomy. Patients with a non-invasive local recurrence or non-lobular histology had a longer time to distant failure or death from other causes than other patients." A presentation by Dr. C. Louis-Sylvestre "A randomized trial comparing axillary dissection and axillary radiotherapy for early breast cancer: 15 year results" concluded that "in early breast cancer with clinically negative lymph nodes, long term survival does not differ after axillary dissection and axillary radiation therapy. Both treatments could thus be considered when a metastatic sentinel node is diagnosed". This was not a randomized trial but a retrospective look at data. There were more cases of lymphedema from the axillary node dissection group but there were complications with both techniques. Dr. S. Kahn presented "Ductal Lavage and Ductoscopy: The Opportunities and the Limitations". As with most techniques, this is not new. It was first discussed in the 1970's. by Otto Sartorius. There is long term data at UCSF. These techniques could be useful in monitoring women at high risk, it might aid in decision-making. More studies are needed to determine which technique might be most useful in particular circumstances. There was some discussion about spontaneous nipple discharges and what might be seen from that. I had such a discharge from one of my nipples in 1981-82 but never thought anything of it. I was diagnosed with Stage 1 invasive lobular carcinoma in January 1993. I am not sure what could have been proposed for me back then if we had these techniques available. We would need therapies that were interruptive of the malignant process (if there is one). Dr. Robert Kuske spoke about "Four or Five day Brachytherapy Instead of Six Weeks of External Beam Radiotherapy in the Treatment of Breast Cancer". This involves implant of radioactive seed 3x1 mm. The vast number of recurrences take place at the site of the original tumor. It was hoped that large-breasted women could benefit from this targeted radiation since otherwise they are exposed to a large radiated area. Another population of interest are those who have been radiated in the past (due to non-Hodgkins lymphoma, etc.). The seeds are planted in the tumor cavity plus 2 cm in all directions beneath and above. A median number would be 19 implanted seeds, in women with tumors of <4cm and those with DCIS. The skin of the breast is much less damaged with this tehcnique and tumor recurrences were less in this study. The goal is a totally painless treatment so they use local pain relief and pain killers including valium and percoset. A less comprehensive dose is delivered to the complete breast but much more directly at the site of the catheter. Thus the greatest dose is directly to the tissue at greatest risk. The subjective QOL is high according to Dr. Kuske. The danger to the "heart and lungs is remarkably better". This is not a good treatment for those with lymph node involvement so patients must be selected. The treatment is delivered for nine minutes in the morning and afternoon. Patients can have a seroma in the breast and still receive this therapy. The long term cosmetic outcome: breast remains soft and full. 4-5 weeks after surgery the wound heals. They are trying to devise ways for doctors to perform this procedure easily. Dr. J. Michael Dixon presented "Extending Breast Conservation" using hormones prior to surgery. Anastrozole, Lestrozole, Exemestane and Tamoxifen. There was a reduction in tumor size in this study population and some evidence of repaired epithelial cells in the breast. There were a small number of local recurrences in the non radiated group and a smaller number if radiation was given. The responses seemed to predict for relative survival and certainly reduced the need for mastectomy. Letrozole was more effective than Tamoxifen in this study. Monica Morrow spoke about "Ablation Techniques for Breast Cancer". The rationale was if the tumor was unrectable (could not be operated upon), or there would be significant operative morbidity (bad results). The technique is done in a brief outpatient procedure. The study was able to show 95% local control, good cosmesis (looked good in the breast) at about 90%. Animal data indicates that radiofrequency ablation, cryoablation (freezing), laser, and high-frequency focused ultrasound are all effective. RFA is done with high frequency into the breast. It is 'frictional heating' and done under a general anesthetic, takes about 30 minutes and achieves complete cell death in about 4/5 patients. In a study of 26 patients, 25 had complete necrosis of the tumor, one person had a complication (2.5 cm full thickness burn). Laser uses direct coagulation of the tumor. The position of the probe is crucial. The tumor must be 1 cm from the chest wall or skin. The surface duration is 20 minutes, under a local IV. 67% achieve complete necrosis. Hematomas (bruising) can obscure the area to place a probe. This technique is best for tumors of 1 cm or less. Common issues are accurate assessement of size and ability to monitor the cosmetic outcome. Patient selection is important and the use of adjuvant therapy is advised. There are lots of errors in the current imaging techniques, both understaging and overstaging. An MRI is best but thereare still problems (at least 6% understaged). Complete characterization of the tumor remains a problem. Apparently fat necrosis is indistinguishable from tumor during imaging. Issues of treatment time, anesthesia and complications are similar to surgery albeit different. Optimal results are achieved in patients with small tumors and meticulous attention needs to be paid to detail. There needs to be well-defined margins from the mammogram. There is NO data to suggest a better outcome than surgery. A smaller incision can be used and it 'sounds' good. However there could be under or over adjuvant treatment due to loss of complete pathology. Still need to know local failure rates, long term cosmetic outcome, cost effectiveness and patient satisfaction. I tried to get information on these techniques for myself. I was dealing with very small tumors on the chest wall. I traveled to Boston's Brigham & Women's Hospital to talk to a doctor there who was using ultrasound-guided laser frequency ablation but was told my 'tiny' tumors were too small for the technique. Monday's Posters: #115 discussed "Quality of life and arm mobility after axillary lymph node dissection versus sentinel lymph node biopsy" A paper from Austria confirmed what we believed to be true-that "Patients who receive SNLB show less pain and better shoulder/arm mobility than patients after ALND. QOL is better in patients with SNLB than in patients with ALND". #125 "The effects of dietary flaxseeds on mammographic density" was unfortunately NOT presented. But the abstract stated that"structural similarities between tamoxifen and mammalian lignan suggest that lignans may have anti-estrogen potential. Therefore, the main objective of this study was to evaluate whether flaxseed can affect mammographic density following long-term, daily ingestion.". Conclusions: "We have previously shown that an anti-proliferative effect of flaxseed by measuring Ki-67 and C-erB-2 labeling index in a preoperative postmenopausal breast cancer study. In this study of premenopausal women mammographic density wasn't altered by radiologist assessement of the scans... Interestingly menstrual cycle length was altered supporting the findings of Phipps W et al and reduction in estrogen synthesis was noted as per the DHEA-S levels. Flaxseed remains of interest to us as a preventive of breast cancer but reduction in breast density in premenopausal women may not be an appropriate surrogate of an anti hormonal effect on the breast at least not by this method for flaxseed in premenopausal women." #149 "Is radiotherapy needed after breast conservation for small invasive breast cancers?" Researchers in the UK looked at a retrospective group of 110 women with "an invasive breast cancer less than 1 cm in size, treated ...by breast conserving surgery." Results: In group 1 the women had received radiotherapy, the median tumor size was 9 (1-10mm) with a median follow up of 74 (15-110) months and had NO local recurrences. Group 2 had not received radiation and with median tumor size of 7 (2-10mm), median follow up of 47 (14-93) months had 6% local recurrence. This paper concluded that "...it may be possible to avoid adjuvant radiotherapy in a subgroup of largely screen detected, node negative patients with invasive tumors less than 1 cm in whome adequate local excision is performed". (Remember that clear margins may really matter in such a population). #151 had a similar topic and came from Japan. "Breast conserving surgery without radiotherapy". This paper noted that "if a strict serial pathological examination of the specimen (every 5 mm) reveals that the case has been successfully resected (negative surgical margins"), they do not treat with radiation. The local recurrence rates were equal to those achieved by teh cases with positive surgical margins who then had radiotherapy. #152 "Reduction of dose to the coronary arteries using IMRT for locoregional post-mastectomy irradiation" came from University of Michigan at Ann Arbor and discussed the fact that "data suggest that adjuvant radiotherapy to the chestwall and regional nodes, including the internal mammary nodes (IMN) improves survival in node positive patients. However, a potential for cardiac toxicity exists given the close proximity of teh IMN to the heart. Therefore, most of the conventional breast and and chestwall treatment techniques either under treat the target volumes (chestwall and IMN) or deliver additional doses to the heart. The concern for cardiac morbidity is further magnified by known cardiac toxicities observed with adjuvant chemotherapies, such as doxorubicin and trastuzumab. A new IMRT technique was developed in order to achieve the same or even lower doses to the heart as the conventional techniques". Conclusion: "IMRT treatment techniques appear to achieve substantial reduction of dose to the main and left anterior descending coronary arteries compared to conventional techniques." #218 "Do breast implants impact on the breast screening programme?" UK researchers report that "Screening women with breast implants is more time consuming and labor intensive than with other women". #233 "Do biological markers expressed by invasive lobular carcimonas account for low response to neoadjuvant chemotherapy?" As remarked upon earlier, this is the beginning of the separation of invasive lobular from invasive ductal. These French researchers report: "We have shown that invasive lobular carcinoma (ILC) has a lower response to neoadjuvant (preoperative) chemotherapy (CT) than invasive ductal carcinoma (IDC). In this study, we analyzed biological markers which may explain such poor response." Their conclusions: " The biological profile of ILC is very different from that of IDC. The low clinical response of ILC to CT could result from its association with markers predictive of low response to CT such as hormonal receptor positivity and a low Ki-67 proliferative index." Some facts: 87% of ILC were found to be ER+ versus only 56% with IDC. PR + was 80% versus 33%, P53 was 0% versus 47% and C-erB-2 positive was 0% versus 33%. Ki-67 rate: median (Q25-75) 5% (2-20) versus 20% (10-40). The results of this study and its conclusions are a bit confusing. In many ways, the profiles of the ILC tumors sound better. They are slower at proliferation, have no P53 problems and are high ER+ and PR+. The problem seems to be these tumors do not respond as well to chemotherapy as the IDC do. I look foward to more studies showing the differences between these two types of breast cancer. #241 "A case-control comparison of risk factors in African-American and Caucasian women presenting with newly diagnosed breast cancer". This study comes from the Cleveland Clinic Foundation (Cleveland, OH). "Although breast cancer mortality is decreasing overall, the mortality in African-American (A-A) women continues to be the highest of all races." A retrospective review of patients from the Cleveland Clinic Breast Cancer database was done. Looking at A-A women versus Cau the conclusion determined that the Gail model does not accurately predict for A-A women. "These data support the concept of modification of the current method of determining risk and/or further investigation into factors which may better predict breast cancer risk in African-American women." #242 "Risk factors for breast cancer aggressiveness" from George Washington University Medical Center deals with the fact that A-A women "more often present with relatively advanced disease and have a shorter survival " than Cau women in whom breast cancer is more common. "Initially thought to be due to poorer access to appropriate health care, some studies have indicated that this shorter survival may be due to the aggressiveness of the tumor. This study investigated risk factors associated with tumor aggressiveness." Conclusion: "We conclude that three factors were found to be associated with tumor aggressiveness: early age at first birth, early age at diagnosis, and long term use of oral contraceptives. It appears that some of the risk factors for developing an aggressive cancer may be different from those for developing breast cancer." #245 "Tables of anticipated benefit from adjuvant therapy for the individual". This discussion comes from the City Hospital, Nottingham, UK. "The relative risk (RR) reductions from adjuvant systemic hormonal (HT) and cytotoxic (CT) therapies are well established, by the meta-analysis process of the Early Breast Cancer Trialists Collaborative Group. However in advising the individual, benefit is best expressed in absolute (AB) rather than relative (RR)." "To estimate AB, the RR reduction from therapy is applied to the patient's prognosis without therapy, with age correction for natural life expectancy. The most sensitive and specific predictor of prognosis is the Nottingham Prognostic Index (NPI)." "For example, for a woman of 45, the AB at ten years from adjuvant polychemotherapy (PCT) is expressed both as a number extra alive (or) as women-years (w-y) gained. Ann's NOTE: It is difficult to reproduce this table so I will summarize. An excellent prognosis with the NPI, and no PCT has a 10 year overall survival of 91%. With PCT there is a 1% advantage and the w-y is 5 years. With a good prognosis, 81% survival and with PCT 3% advantage and 15 w-y gained. With a moderate I prognosis, 71%, with PCT a 5% advantage is gained with 25 w-y. A poor prognosis has a 39% overall survival with an 8% advantage using PCT and 55 w-y gained. A very poor prognosis has an 18% 10 year overall survival rate, with a 16% advantage in using PCT and a gain of 80 w-y. "A woman in the very poor prognosis group receiving TAM (tamoxifen) stands to gain an average 9 month extra of life (or) doubles her chance of 10 year survival. A woman in the excellent prognosis group gains 1 month average (or) only a 1% improved 10 year survival chance. As in previous years, German researchers presented their data on "Level-I evidence for prognostic and predictive impact of uPa and PAI-1 in node-negative breast cancer provided by second scheduled analysis of multicenter Chemo-N0 therapy trial". Ann's NOTE: There may be more here Delivered at SHARE in conjunction with other reports (very shortened) Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.