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Updates from #ASBrS19

6 March 2019

The American Society of Breast Surgeons (ASBrS) held their annual meeting in Dallas last week. This meeting usually draws about 1500 breast surgeons (just under half the ASBrS membership) from around the world, for several days of pre-meeting courses, didactic sessions, and research presentations. In addition to the science, the meeting provides opportunities for breast surgeons in all types of practice settings and at all levels of training and practice to network and learn from each other. 

The following covers some highlights from the general session. 

The meeting started off with the Critical Issues in Breast Cancer Forum: Changing Paradigms for Breast Cancer Surgery. Dr. Cary Kaufman presented an update on current clinical trials for cryoablation for breast cancer. Cryoablation is a technique that freezes the tumor, using a small probe placed into the tumor (similar to a needle biopsy) under local anesthesia. There are several types of ablative therapy including laser, radiofrequency, high-frequency ultrasound, and cryoablation. Because cold is a natural anesthetic agent, patients undergoing cryoablation do not need any sedation, and the procedure is performed while they are awake. 

Cryoablation was initially tried with benign tumors (fibroadenomas). In many cases, the fibroadenoma reabsorbed, leaving no mass and only a tiny (3 millimeter) scar. Multiple studies have looked at the use of cryoablation for breast cancer, and most have restricted therapy to patients with small (1.5 cm or smaller) estrogen receptor positive, Her2/neu negative tumors. I participated in a national multi-center trial, the ACOSOG / ALLIANCE Z1072 trial, which was published in 2016 and demonstrated that cryoablation was successful in the majority of these patients. All patients in the ACOSOG / ALLIANCE Z1072 study underwent surgery within one month of the ablation, so that the tumor site could be removed and evaluated. Several subsequent studies have looked at cryoablation for breast cancer without surgery. The longest follow up was from Dr. Fukuma in Japan. After 12 years of follow up, he reported 3 local (in-breast) recurrences in 304 patients. Combining 3 published trials, Dr. Kaufman noted that local recurrence rates range from 0.98 – 1.4%, and he concluded that this is extremely promising technology. He also noted that cryoablation of breast cancer appears to have an immunologic benefit – when the tumor cell membranes are disrupted by the extreme cold, the patient is exposed to tumor antigens, which may prompt antibody formation. It is very premature to determine if this immunologic effect will help reduce recurrence rates.

Dr. William Small presented updates on 3 clinical trials of intraoperative radiation therapy (IORT). An advantage of IORT is that it is delivered at the time of lumpectomy, in the operating room, as a one-time treatment. A disadvantage is that status of the lumpectomy specimen margin and lymph nodes are not known at that time. If it is found on final pathology that there are positive margins, external beam radiation is recommended, and at least one trial noted that approximately 30% of patients who received IORT required additional whole breast radiation. Most studies of IORT have been limited to “low risk” lesions – small, low grade invasive cancers in older women. He discussed that a criticism of these studies is that some of these women may not have needed radiation therapy at all. Dr. Small noted that local recurrence rates are slightly higher (3.3 versus 1.3%) but that statistically, IORT is considered “non-inferior” to whole breast irradiation. He noted that seroma (fluid accumulation) is more common in patients who undergo IORT.  He concluded by stating that there is an “acceptable” toxicity, with non-inferior local recurrence. However, as there is relatively short follow up available in low risk patients, he questioned the applicability of this procedure to a broader patient population. A US registry is planned.

Dr. Antonio Toesca presented the results of his study of 100 patients who underwent robotic nipple sparing mastectomy (NSM) and implant reconstruction, and showed a fascinating video which highlighted the precise and meticulous dissection, along with improved visualization, compared to a standard surgical procedure. The average incision size was a little over 1 inch, and the specimen was removed intact (in one piece). The procedure averaged 1 hour and 18 minutes longer than their standard for a nipple sparing mastectomy and implant reconstruction (3 hours, 36 minutes for the robotic procedure. Patients who underwent the robotic procedure were less likely to have axillary web syndrome and reported Improved physical, psychological and sexual well-being. 

Why could performance of NSM using robotic technology become important? Dr. Tina Hieken presented the results of her study (abstract 580759, page 31) showing that as experience with the procedure has grown, indications are expanding and patients who previously were not candidates for the procedure are now being considered. A NSM is a technically challenging procedure, and it takes a toll on the neck and back of a surgeon. A 2017 study published in JAMA Surgery noted a high incidence of work-related musculoskeletal disorders among surgeons and interventionists. Dr. Katherine Kopkash presented her research (abstract 51837, page 52) using intraoperative electromyography (EMG) on the surgeon to assess muscle strain during NSM. Of course, oncologic safety is the primary concern, and more study on the long-term outcomes (as well as costs) of robotic procedures is required. 

The next session was Emerging Strategies in Breast Cancer Care, which focused on “de-escalation” of surgical therapy. Dr. Anna Weiss provided an update of clinical trials evaluating active surveillance for low-risk ductal carcinoma in-situ (DCIS): COMET, LORD and LORIS. Approximately 60,000 cases of DCIS are diagnosed annually. Patients undergoing active surveillance do not have surgery, some are treated with endocrine therapy, and all undergo regular monitoring. This is a accepted option in select cases of prostate cancer, and Dr. Weiss noted that there is no difference in overall survival in patients with low-grade DCIS who do not undergo treatment. The LORD and LORIS trials are open in the UK and the COMET study is open in the US. (Additional perspective)

Dr. Henry Kuerer presented his research on the percutaneous management of breast cancer in the setting of a pathology complete response (pCR) following neoaduvant (before surgery) chemotherapy. He noted that for survival and recurrence matter most, but side effects and complications are significant concerns for both patients and physicians. I’ve recently covered details of his research on this blog. 

Some of the twitter conversation related to this talk included patients who noted that they would rather undergo surgery than chemotherapy. It is important to note that the patients involved in this study are those who were going to be treated with chemotherapy regardless of surgical therapy because they have triple negative or Her2/neu positive breast cancer. In these patients, systemic (whole-body) therapy is necessary due to the higher likelihood of metastatic disease. Surgical therapy in these patients, especially the “exceptional responders”, may not improve outcomes, but of course more study is needed. Surgery remains the standard of care for breast cancer therapy.

Dr. Judy Boughey discussed several cooperative group trials evaluating management of the axillary (underarm) lymph nodes, and these studies are also focusing on how we can safely de-escalate axillary surgical therapy after neoadjuvant chemotherapy. This is an area that is rapidly evolving with expansion of the criteria for a less aggressive approach to the axilla.

In a session on Evidence-Based Prevention and Management of Surgical Complications, Dr. Suzanne Klimberg presented on chronic post-mastectomy seroma. A seroma is a fluid collection – fluid normally accumulates after mastectomy which is why drainage tubes are left in place. Normally, drains can be removed after 7-14 days, but about 30% of patients will develop prolonged drainage. This is a frustrating problem for patients and physicians as the persistent fluid can be uncomfortable, may increase the risk of infection, and may delay the start of planned chemotherapy or radiation. She noted that a surgical technique to close the tissue known as “quilting” can reduce the rate of chronic seroma, but that it results in excessive skin dimpling and has a significant impact on the cosmetic results. She stated that additional drainage tubes, various “sealant” agents and compression (such as wearing an ace wrap) are not effective. The area may be sclerosed (scarred) by instilling talc or antibiotics, and in some cases, re-operation to remove the inflamed tissue is indicated. Otherwise she recommended patience and repeat aspirations. She noted that there are no ways to successfully prevent seromas from forming.

Dr. Amal Khoury presented on chronic post-mastectomy pain, and noted that persistent pain occurs in 25-60% of patients undergoing any type of breast surgery. It is thought that this chronic and at times severe pain is due to damage to and neuroma formation of the cutaneous (skin) branches of nerves that run along the 4thand 5thribs, which are roughly at the inframammary fold (bra line below the breast). These cutaneous nerve branches are often not visible at the time of surgery. She noted that the pain syndrome it is often not recognized, and when recognized it is often not treated effectively. She stated that injections with a combination of long-acting local anesthetic and steroid (in a very small dose) at the trigger points is more effective than taking pain or other medications, and in their study at UCSF, 91% of patients required only one injection for lasting relief.

The next session was Practical Considerations for Systemic Treatment. Dr. Judy Boughey reviewed the I-SPY2 clinical trials, which utilize an innovative “adaptive randomization” approach in patients who are undergoing neoadjuvant chemotherapy for triple negative, Her2/neu positive, or other high risk breast cancers. pCR rates are assessed, and drugs that are successful move up higher in the randomization algorithm. This study and its flexible randomization protocol have accelerated the use of some novel agents. Patient reported outcomes assessing quality of life, fear of recurrence, symptoms and side effects are being assessed. If drug response rates are similar, the “winner” may be the one associated with fewer side effects. Dr. Barry Rosen discussed specific strategies to identify the previously involved axillary lymph nodes when chemotherapy is performed prior to surgery. Dr. Elizabeth Mittendorf presented on breast cancer immunotherapy and surgical implications of these treatments. She noted that one agent, atezolizumab, is currently approved for use in patients with metastatic triple negative breast cancer. She noted that there are concerns about wound healing complications with these agents but unfortunately the clinical trials did not specifically assess for this. In addition, she noted that some immunotherapy agents are associated with development of adrenal insufficiency – this complication has only been reported in a small percentage of patients, but it is an important consideration in any patient who is going to have surgery.

A session was held on breast imaging. Dr. Molly Sebastian presented on the impact of breast density on breast cancer risk, noting that it is more difficult to screen patients with dense breasts, and that these patients are also at increased risk for developing breast cancer. The associated breast cancer risk increases with the level of density. Approximately 50% of women in US are considered to have dense breast by mammogram, and she cited a 2010 study that found that 30% of breast cancers could be linked to highly dense breast tissue. Contributors to increased density include younger age, use of hormone replacement therapy, race (Asian), diet (Western), alcohol use, and hereditary factors. She did stress that the presence of a germline genetic mutation (such as BRCA 1/2) conveys a much higher level of risk (regardless of density) than breast density itself. 

Dr. Brigid Killelea discussed balancing high-risk screening (which usually includes MRI) with the concerns about gadolinium toxicity. Gadolinium is a “rare earth heavy metal”, and is used in the contrast material that is administered (using an intravenous line) when breast MRI is performed. Acute allergic reactions are uncommon but as gadolinium is excreted through the kidneys, there are concerns about the potential for kidney damage especially in patients with pre-existing renal insufficiency. Nephrogenic systemic fibrosis (NSF) is an unusual condition that results in progressive deposition of gadolinium in the skin. It has also been found that the number of exposures to the linear form of gadolinium (as opposed to macrocyclic, which is what is most commonly used with breast MRI) correlates with increasing deposits in the brain. More research is needed to determine if this leads to an increased risk of Parkinson’s or other diseases. Studies evaluating “fast” MRI protocols are ongoing but they still use gadolinium contrast. Some work is being done with non-contrast MRI and Dr. Killelea noted that it shows some promise in detecting certain lesions. 

In the session on Ethical Issues in Breast Cancer Surgery, Dr. Rachel Greenup discussed how to manage the situation when the principles of respect for patient autonomy conflict with the standard of care. She noted that patient autonomy allows for us (as physicians) to educate but not to decide care for patients, and that poor physician-patient communication is a key factor in patients opting for non-standard care. Factors associated with patients declining standard therapy include a negative first experience, an uncaring / insensitive / unnecessarily harsh oncologist, fear of side effects, and belief in the efficacy of alternative therapy.  In regards to endocrine therapy for breast cancer, she noted that unmanaged side effects are a significant contributor to stopping therapy. She also presented data showing poorer outcomes in patients who declined standard therapy, and that many, when faced with disease progression, did then opt for conventional treatment. She recommended that physicians review and present evidence to their patients in an understandable way, taking time to acknowledge fears and address patient barriers to treatment, provide time to adjust to diagnosis, suggest a 2ndopinion, and avoid abandonment or fear tactics. She also suggested that physicians be more open (when medically safe) to the combination of alternative and standard therapy. She stressed that patient autonomy is the priority, and that open communication can help align patient-centered care with evidence-based care. 

Dr. Terry Sarantou discussed the ethical issues of obtaining informed consent when performing a new surgical procedure, noting that there is FDA oversight for new drugs and surgical devices, but not for surgical procedures. He stressed that informed consent is a communication process, not a form to be signed. 

Recognizing the role that surgeons play in the current opioid crisis, Dr. Sarah DeSnyder discussed proper prescribing of narcotics in breast surgery. There was also an abstract presentation by Dr. Betty Fan (abstract 5808940, page 27) on this subject. She noted that women who expected postoperative pain or those who reported higher preoperative distress used more postoperative opioids for pain management. She stressed that physician and trainee education about proper prescribing is critical as is setting patient expectations for postoperative pain and providing non-narcotic options. The use of nerve blocks, long-acting local anesthetic agents, acetaminophen (Tylenol) and ibuprofen were also discussed. 

Photographs are an important part of breast and reconstructive surgery to document results both for patient and physician education as well as for quality assurance, and Dr. Toan Nguyen reviewed some of the ethical, legal and technical considerations to protect patient confidentiality and privacy. The ASBrS statement on this issue has been published in the Annals of Surgical Oncology.

In the session covering New Perspectives on Old Problems, Dr. Lee Wilke noted that with improved surgical techniques, breast conservation is now appropriate for select patients with more than one tumor in the breast. She did note that in up to 20-30% of patients with more than one tumor in the breast, the tumors are different subtypes, which may have implications for therapy – so pathologic analysis needs to be performed on all lesions. Dr. Stephen Grobmyer reviewed the current literature on local (in-breast) recurrence, noting that repeat breast conservation may be appropriate in some patients. However, if repeat radiation is performed, there is a higher risk of skin toxicity and potentially unacceptable cosmetic results. In addition, for left-sided breast cancers, repeat radiation raises concerns about cumulative radiation damage to the heart. Repeat lumpectomy without radiation is associated with a 20-40% risk of local recurrence. IORT may be utilized in some patients, but studies are ongoing and data is limited.

Dr. David Euhus discussed that genetic testing does not only potentially impact the surgical procedure that is recommended, but may influence the decision for radiation therapy as well as systemic therapy. In addition, results of genetic testing may impact surveillance for additional breast or other cancers in the patient as well as recommendations for family members. The ASBrS recently updated their genetic testing guideline, recommending that genetic testing be considered for newly diagnosed breast cancer patients. (Additional perspective)

In the session on Benign Breast Disease, Dr. Jane Mendez reviewed breast fistulas (persistent drainage through the skin) and infections, and Dr. Vincent Reid reviewed some of the non-malignant masses that can develop in the male breast. Dr. Katrina Mitchell, who is a breast surgeon as well as a certified lactation consultant, provided recommendations for management of post-partum patients who develop mastitis or breast abscess. One of the key recommendations was that patients should continue breast feeding (better than pumping for keeping the breast empty) and that patients do not need to “pump and dump” the milk while on antibiotics. 

Dr. Stephanie Valente discussed breast pain, which is a common problem that frustrates both patients and physicians. Pain is a symptom of breast cancer in less than 2% of cases.  Suggestions for treatment include decrease caffeine, nicotine, and dietary fat intake, and consider supplementation with essential fatty acids such as evening primrose oil (EPO) or vitamin E. However, she noted that that some studies show that EPO and vitamin E are no better than placebo. Both flaxseed and chasteberry have shown to be effective. Diclofenac (a non-narcotic pain medication) gel can be effective but it needs to be used for several weeks before improvement is seen and it is expensive. In severe cases, danazol (an androgen hormone) or tamoxifen can be used but are associated with significant side effects.

There were several sessions on oncoplastic surgery. Oncoplastics refers to combining oncologic (cancer) surgery with attention to cosmetic outcomes. Basic principles include placing the incision in the least conspicuous place and closure of as much of the breast tissue once the tumor has been removed as possible to minimize, or preferably avoid, a depression in the area. More advanced techniques include rotation flaps and mastopexy (lift) that may be performed by breast surgeons or breast surgeons collaborating with their plastic surgical colleagues. There was also a session discussing some of the advanced microvascular procedures that are being studied to treat lymphedema as well as a video session showing some basic techniques to perform a better (flat) closure for patients undergoing mastectomy without reconstruction. 

The keynote address was delivered by the actress Kathy Bates. Ms. Bates underwent a bilateral mastectomy for breast cancer and has bilateral arm lymphedema. She is a spokeswoman for the Lymphatic Education and Research Network, working to educate, support, and advocate for patients who have lymphedema. She delivered a moving and unique address to the group, combining science and her personal patient perspective. An abstract (abstract 581304, page 22) presented during the meeting demonstrated that postoperative surveillance with bioimpedence spectroscopy compared to tape measure resulted in a 10% decrease in the number of patients requiring complex decongestive physiotherapy. However, these results, which were a planned interim data analysis, did not reach statistical significance.

The new ASBrS screening mammography guidelines were released at the meeting. They recommend formal risk assessment starting at age 25 and a risk-based approach to screening, as well as annual mammography starting at age 40 for average-risk women. (Additional commentary)

All of the research abstracts and posters can be found here. There were many interesting and thought-providing presentations, but it is important to remember that abstracts represent incomplete data and have not been subject to the peer-review process. The oral abstracts that were presented will be published in manuscript form later this year. The poster gallery can be found here (not all posters have been uploaded by the presenters).

As usual if anyone is interested in one of the articles referenced but does not have access, or wants additional information, please send your email address to me: contact at drattai dot com and I will be happy to respond.

This post has not been endorsed by the American Society of Breast Surgeons.

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Highlights from the 2018 American Society of Breast Surgeons Annual Meeting

10 May 2018

The American Society of Breast Surgeons held their Annual Meeting in Orlando, FL from May 2nd – 6th. As usual, it was well attended – the meeting is known for being very practical and full of information that breast surgeons can bring back to their practices to help improve patient care.

I’ve picked a few topics to highlight in this post: Genetics, Imaging, Local Therapy, Systemic Therapy, Immunotherapy, Liquid Biopsy, Diet and Hormone Therapy, and Changing Paradigms. The following are comments expressed by the meeting speakers. My own comments will be noted in bold italics.

Genetics:

  • BRCA 1 mutation carriers are more likely to have triple negative breast cancer.
  • BRCA 2 mutation carriers are more likely to have ER positive, Her2/neu negative breast cancers.
  • The risk of a 2nd breast cancer in BRCA mutation carriers on average is about 2% per year depending on the specific mutation and the age of affected relatives. It can approach 60-80% in some patients. This increased risk of a new breast cancer is why bilateral mastectomy is often recommended. Removal of the opposite breast may result in improved overall survival but results from studies are mixed.
  • For BRCA mutation carriers, it is recommended that clinical breast exam (breast exam by the physician) be performed every 6-12 months. From age 25-29 annual MRI is recommended, and from age 30-75 annual mammogram (3D mammogram or tomosynthesis was recommended) along with MRI was recommended. It was stated that this screening regimen has not been shown to improve survival, but the screen-detected cancers were less likely to have lymph node involvement. No specific recommendation was made for imaging or exam after bilateral mastectomy.
  • MRI every 6 months has been suggested by some, but there are concerns about gadolinium (a heavy metal material which is the contrast agent used for breast MRI) buildup.
  • Removal of the ovaries is recommended around age 40.
  • In patients with BRCA mutations who undergo salpingo-oophorectomy (removal of the ovaries and fallopian tubes), estrogen replacement therapy has not been shown to increase subsequent breast cancer risk. However, combined estrogen / progesterone therapy may increase subsequent breast cancer risk. It was suggested to consider removing the uterus at the time of ovary removal, so that estrogen alone could be used (if the uterus is not removed, estrogen alone could increase the risk of uterine cancer).
  • There are many other genetic mutations that have been identified that have a variable association with increased breast cancer risk. It was stressed that family history and other factors need to be considered when these less common mutations (such as CHEK2, ATM, PALB2 and many more) are present, before recommending mastectomy.
  • It was stressed that the presence of a variant of unknown significance (VUS) should NOT prompt aggressive surgery.
  • A study was presented that demonstrated that current breast cancer genetic testing guidelines exclude almost half of high-risk patients, and a recommendation was made for testing of all breast cancer patients regardless of age, family history or other factors.

Breast Imaging:

  • Dense breast (as determined by mammogram) reduces the sensitivity of mammograms, and also is associated with an increased risk of breast cancer.
  • It was stressed that determination of breast density is subjective and studies have shown significant variability in grading of breast density. Automated methods of assessing density are being evaluated.
  • 34 states have dense breast notification legislation. Some have supplemental screening (such as ultrasound) legislation (California does not).
  • An advantage of tomosynthesis (also known as 3D mammogram) in patients with dense breasts is that it decreases the likelihood of callbacks and improves the cancer detection rate
  • Abbreviated (3 minute scan) MRI shows promise for screening.
  • There is an ECOG/ACRIN study planned which will evaluate abbreviated MRI versus tomosynthesis in women with dense breasts.
  • Contrast-enhanced mammography is superior to digital mammography but it requires an IV contrast dye, and there is currently no ability to biopsy lesions seen only with this technique.
  • It was stressed that automated whole breast ultrasound (ABUS) should not replace mammography.
  • Molecular breast imaging has a much higher radiation dose due to the need to inject a radioactive material and cost is higher than other imaging modalities. There are only about 100 units in the US.
  • In addition to BRCA mutation carriers, patients who have a history of chest wall radiation at a young age (most commonly for treatment of Hodgkin’s lymphoma) or those who have a lifetime risk of breast cancer over 20% (assessed by various computer modes) should have annual MRI in addition to mammograms for surveillance.

Loco-Regional (breast and underarm lymph nodes) Therapy:

  • Recurrence of cancer in the breast (known as a local recurrence) was previously thought to be related to “disease burden” – the amount of tumor and size of clear margins. According to Dr. Monica Morrow, this has led to an “obsession” with margins, wider surgical resection than necessary, and the overuse of MRI.
  • Due to improvements in systemic therapy (chemotherapy and endocrine therapy), local recurrences have decreased over time.
  • Local recurrences are largely a function of tumor biology – more aggressive tumor types are more likely to recur. Bigger surgery does not overcome bad biology.
  • The rates of contralateral (opposite side) new breast cancer have been decreasing in the US; currently <1% at 5 years for patients who do not have a genetic mutation.
  • Updated 2018 ASTRO guidelines endorse hypofractionation (a shorter course of radiation therapy) in a larger group of patients.
  • There are 3 trials that will evaluate whether or not radiation therapy can be avoided in selected patients – LUMINA, IDEA and PRECISION.
  • ~30% of patients undergoing “direct to implant” reconstruction (no temporary tissue expander) need a second surgery. One of the plastic surgeons that I work with notes that “reconstruction is a process not a procedure!”
  • Managing expectations of the reconstruction process is important so patients don’t get frustrated and feel like their reconstruction has “failed.”
  • Post mastectomy radiation worsens outcome from implant reconstruction; severe capsular contracture occurs in about 30% of patients.
  • If radiation is performed on the permanent implant instead of the tissue expander, the rate of reconstruction failure goes down by 50%.
  • Many plastic surgeons prefer that autologous (patient’s own body) reconstruction be performed after radiation to avoid shrinkage of the flap. A tissue expander could be placed at the time of mastectomy which will be removed after radiation when the flap procedure is performed.
  • Lymphedema risk is about 25% with axillary node dissection versus 6-8% with sentinel node biopsy. In certain patients over age 70 with ER+ breast cancer, sentinel node biopsy can be avoided – this was also covered in the Society of Surgical Oncology’s Choosing Wisely statements. However, it is also important to take into account whether or not the patient will be treated with radiation and/or endocrine therapy. Sentinel node biopsy is also not recommended for most patients undergoing lumpectomy for DCIS. The SOUND trial is evaluating the use of axillary ultrasound to try to determine if this can help select patients who do not need sentinel node biopsy.

 Systemic Therapy:

  • The use of genomic tumor testing could avoid the use of ineffective (for the specific patient depending on tumor profile) chemotherapy in up to 50,000 patients per year.
  • Neoadjuvant (before surgery) chemotherapy is most commonly used to decrease tumor size so that patients have a higher likelihood of being able to undergo lumpectomy instead of mastectomy.
  • About 50% of patients who have positive lymph nodes before chemotherapy are converted to node-negative due to chemotherapy prior to surgery, and they may be able to avoid full axillary node dissection.
  • Response to neoadjuvant chemotherapy varies by tumor subtype. Her2/neu and triple negative breast cancers are more likely to respond compared to ER+ and Her2/neu negative tumors.
  • Technical considerations to improve the accuracy of sentinel node biopsy after neoadjuvant chemotherapy including the use of 2 dye agents to map the nodes and removal of at least 3 lymph nodes.
  • A multidisciplinary approach for management of patients who are being considered for neoadjuvant chemotherapy was stressed.
  • Recurrence patterns are different for ER+ versus ER- disease. Patients with ER+ breast cancer are at risk for late recurrence, even 20 years after treatment – the highest risk is in patients with multiple involved lymph nodes. Patients with ER- disease tend to recur earlier (within the first 2-5 years), and then the likelihood of recurrence decreases.
  • Recurrence in the breast is a marker of increased risk for development of metastatic disease.
  • Premenopausal patients who have “low risk” disease could consider stopping tamoxifen after 5 years. It is recommended that patients with “high risk” disease consider 10 years of tamoxifen therapy.
  • Postmenopausal patients who are considered “high risk” could consider 10 years of an aromatase inhibitor, although there is not currently data that shows this approach improves survival. Prolonged therapy in these patients does reduce the likelihood of developing a new breast cancer and reduces the likelihood of breast cancer recurrence.

Immunotherapy / Liquid Biopsy:

  • A brief session was held covering immunotherapy and liquid biopsy.
  • Immunotherapy for breast cancer has not had the success seen in melanoma, lung cancer, colon cancer and bladder cancer.
  • The combination of chemotherapy and a modified herpes virus has shown some promise in patients with triple negative breast cancer.
  • It is likely that immunotherapy treatments will vary depending on tumor subtype.
  • Circulating tumor DNA may predict metastatic disease 8-12 months before evidence of tumor spread – but we are not yet able to improve patient outcomes based on this information. Therefore, circulating tumor cell and circulating cancer cell DNA assessments are not recommended for routine clinical use.
  • It was predicted that “liquid biopsy” will eventually be used routinely to help manage breast cancer patients.

 

Diet and Hormone Replacement Therapy:

  • A low fat diet improved the likelihood of death from breast cancer only in obese women.
  • Currently there is more information regarding the impact of dietary fat versus dietary sugar on breast cancer risk. Dr. Rowan Chlebowski, who has been a lead author on the Women’s Health Initiative studies, stated that due to an increasing number of reports suggesting that sugar may impact breast cancer development, they plan to look more closely at this.
  • Insulin resistance is associated with cancer specific and all-cause mortality in postmenopausal women.
  • One of Dr. Chlebowski’s conclusions was to “avoid body fatness.” Unfortunately, specific guidance on how to best accomplish this was not discussed!
  • The risk of breast cancer associated with hormone replacement therapy (HRT) is greater if it is started around the time of menopause versus 3-5 years later.
  • Breast cancer risk in women taking HRT is higher in women with extremely dense breast versus fatty replaced breasts. The biggest risk from HRT is in lean women with extremely dense breasts. The lowest risk from HRT is in women with a body mass index (BMI) > 35 with fatty replaced breasts.
  • Combination estrogen / progesterone HRT should be avoided in lean (BMI <25) women especially if they have dense breast tissue.
  • The Black Women’s Health Study found no increased breast cancer risk if HRT use was <10 years, but cancer risk was increased if use was >10 years. Other studies showed either no risk or no association of risk from HRT with race.

 

Changing Paradigms – Avoiding Surgery for DCIS and Neoadjuvant Patients

  • Active surveillance is being evaluated for ductal carcinoma in-situ (DCIS). Over 60,000 cases of DCIS are diagnosed per year in the US. Not all cases of DCIS will progress to invasive cancer, and the likelihood of progression is lowest in low grade DCIS. In these patients, less than 10% develop invasive cancer in the same breast after 10 years and over 20% die from other causes within 10 years of diagnosis.
  • There are 3 ongoing clinical trials are evaluating active surveillance for low risk DCIS (LORIS, LORD, and COMET). The COMET trial is the only study open in the US. DCISOptions.org has additional information about DCIS and the COMET trial.
  • Some patients who undergo chemotherapy prior to surgery are found to have no residual tumor after the area has been removed, termed pathologic complete response (pCR).
  • Prompted by patients asking “why do I need surgery?” if it appears that all cancer has resolved after chemotherapy, researchers at MD Anderson Cancer Center are evaluating whether surgery can be omitted in patients who appear to have a pCR after chemotherapy. Patients who have no apparent tumor based on post-chemotherapy imaging (including MRI) undergo core needle biopsies. If these biopsies show no tumor, patients taking part in the study will undergo radiation without surgery.
  • Similar studies are taking place in the Netherlands, Germany, and the UK.
  • Henry Kuerer from MD Anderson stated that “surgeons have an obligation to study possibility of no surgery – and we must ensure safety and efficacy with well-designed trials.
  • Several types of ablative therapy (destroying the tumor without surgery) are being evaluated including cryoablation (freezing), laser, and transcutaneous (no needle puncture or scar) high frequency ultrasound.

Lifetime Achievement Award

Dr. Ernie Bodai, the breast surgeon who spearheaded the Breast Cancer Research Stamp, was honored with a lifetime achievement award. It was fascinating to hear his story and how one man (with a little help) got congress to change a law.

This post has not been endorsed by the American Society of Breast Surgeons

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Updates from ASBrS 2017

8 May 2017

As a past-president of the American Society of Breast Surgeons I am probably more than a little biased. However, as always, the annual meeting held April 26-30th in Las Vegas was terrific. Topics including the full spectrum of breast disease, including benign and high risk lesions, genetic testing, breast cancer diagnosis and treatment including medical and radiation oncology updates, and metastatic disease.

The press briefing highlighted 3 abstracts which showed that:

  • Modern therapy for inflammatory breast cancer is associated with better outcomes than historically seen
  • Post-treatment lymphedema is related to a combination of treatments including surgery, radiation therapy, and chemotherapy – not just from surgery
  • Patients with DCIS have a 5 year risk of developing a cancer in the other breast of 2.8% and a 10 year risk of 5.6%, and patients should be discouraged from undergoing bilateral mastectomy for this condition. Developing a new cancer in the previously treated breast was twice as likely as developing a new cancer in the opposite breast, and the use of tamoxifen reduced the likelihood of any recurrence.

Dr. Nathalie Johnson moderated a pre-meeting course on Building a Breast Cancer Survivorship Program. I was invited to speak on Traditional Versus Virtual – Options for Patient Support and Education. Just as it can be challenging to choose between cake and ice cream (2 really good things), patients note advantages to both in person and online support and education. It doesn’t have to be one or the other – do what works for YOU! My slides are posted on SlideShare.

During the general sessions, a few topics stood out to me:

Dr. Shelley Hwang from Duke University spoke on DCIS subtyping and overtreatment. She noted that DCIS now comprises over 20% of all mammographically detected breast cancer. It is considered a “non-obligate precursor” of invasive cancer – the rate and likelihood of progression to invasive cancer are not clearly known. However, it is clear that some patients will never exhibit progression to invasive disease, and she discussed this in the context of thyroid and prostate cancer – two situations where we know that treatment in some patients will not provide the patient any benefit. The challenge is to sort out which patients will benefit from treatment and which ones will not. The COMET study is currently enrolling patients with low grade DCIS to in an attempt to help answer these questions.

Dr. Virginia Herrmann from Washington University in St. Louis spoke on non-genetic breast cancer risk factors. This is an important topic and I believe one that doesn’t get covered enough. She noted that hormone replacement therapy does increase risk – although the incremental risk is small and is seen only after about 5 years of use. However, longer term use does result in higher risk. Increased body mass index (BMI) is associated with risk – the risk of breast cancer is 30% higher in patients with a BMI greater than 31 kg/m2 compared to a BMI of 20 kg/m2. She noted that there is a linear relationship between alcohol intake and cancer risk, noting a 10% increase in risk for each 10 gm/day (for wine this is a little over 3 oz) increment in alcohol consumption. The risk is most associated with post-menopausal breast cancer, although in the study she quoted, only alcohol intake during age 50s was associated with an increased risk of postmenopausal breast cancer. She noted the association of ionizing radiation and breast cancer, and young women who received mantle (chest area) radiation for Hodgkin’s lymphoma have a markedly increased risk for developing breast cancer. She noted that breast cancer risk is increased in smokers, correlated with smoking intensity and duration. Finally, she noted the increased risk of breast cancer among soldiers stationed at Camp LeJune related to contaminated drinking water (tetrachloroethylene and trichloroethylene).

Dr. Tiffany Traina, a Memorial Sloan Kettering medical oncologist, gave a brief presentation about triple negative breast cancer: Searching For the Magic Bullet. There are several promising treatment strategies including targeting androgen receptors, the use of PARP-inhibitors in patients who have BRCA gene mutations, antibody-drug conjugates, immune modulating approaches, and targeted therapies based on tumor genomic profiles. Stay tuned – much more to come over the next few years related to this aggressive breast cancer subtype.

Dr. Lisa Newman, from the Henry Ford Health System in Detroit, spoke on Breast Cancer Outcomes: Disparities versus Biology. I have heard her speak on this topic multiple times over the years and always enjoy her excellent presentations. She noted that the incidence of breast cancer in black women is increasing, now close to that in white women. However, mortality rates for black women are higher than those for white women. There is an increased frequency of triple negative breast cancer in black women. She is involved in a research initiative evaluating the association between African ancestry and high risk breast cancer in white American women, African American women, and women in Ghana, including studying novel aspects of tumor biology and breast cancer stem cells – she is asking the question “are there differences in the oncogenic potential of mammary tissue that are associated with ancestry”? She concluded with what I felt was a powerful slide – 60% – 43% – 20%. Those were the survival rates for passengers on the Titanic who were in 1st – 2nd – 3rd class. She noted that healthcare outcomes are often dependent on access to care, and ended with a quote from Dr. Martin Luther King, Jr.: “Of all the forms of injustice, inequality in health care is the most shocking and inhumane”.

Dr. Stephen Edge, from the Roswell Park Cancer Institute, gave an update on the new American Joint Commission on Cancer staging system (AJCC 8th edition). Currently we stage breast cancer based on tumor size and lymph node status. However, it is recognized that that tumor biology plays an important role in prognosis and in some patients it may be more important that tumor size. The new staging system will incorporate tumor grade, Her2/neu status, ER/PR status, and Oncotype Dx status (if available) and should more accurately reflect prognosis. There are 422 lines in the new staging system – it will be impossible to memorize! Thankfully, he noted that the AJCC is working on a staging app.

The last day of the meeting held some great sessions, and the meeting room remained packed up until the very last minute. Dr. Ann Partridge from Dana Farber discussed special considerations in the young breast cancer patient. She noted that the disease is different, the patients are different, and the treatments should be different. Younger women have a higher likelihood to have more aggressive subtypes such as Her2/neu over-expressed and triple negative, and have lower survival rates than older women – even in those with the ER positive breast cancer. However, she cautioned not to over-treat patients based only on age. She noted that young age is not a contraindication for breast conservation, and that there is no clear improvement in mortality in patients who undergo more extensive surgery. She noted the need for improvements in treatment and support, including focused research and guidelines, which should lead to better outcomes.

Dr. Irene Wapnir from Stanford spoke on fertility preservation issues. She noted the various fertility options including medications and procedures. She also reviewed the POSITIVE trial, which will be assessing the risk of breast cancer relapse in patients who temporarily stop endocrine therapy to permit pregnancy, as well as to evaluate factors associated with successful pregnancy after interruption of endocrine therapy. She also stressed that fertility preservation should be discussed with any woman of childbearing age, whether or not she has had a prior pregnancy or a child – physicians won’t know what is important to their patients unless we ask!

Dr. Katherina Zabicki Calvillo from Dana Farber discussed breast cancer in pregnancy. She noted that 0.2-4.0% of breast cancers are diagnosed in pregnant patients – about 1 in 3000 pregnancies. She also noted that given the overall delay in childbearing (and the association of increasing age with breast cancer), the incidence of pregnancy-associated breast cancer will increase. Delays in diagnosis are related to hormonal changes which affect breast tissue making the exam more challenging, and that many patients and physicians assume that masses are related to pregnancy. She stressed that pregnancy termination is usually NOT required, but a multidisciplinary team approach is required. Many of these patients present in more advanced stages, but stage-for-stage, the prognosis is similar to non-pregnant patients with breast cancer. Chemotherapy can be given after the first trimester, but hormonal and Her2/neu targeted therapy should be avoided. She noted that mastectomy should be performed in the first and early 2nd trimester, and discussed the challenges of immediate reconstruction. Breast conservation could be considered in the late 2nd or 3rd trimester with post-lumpectomy radiation planned for after delivery.

Dr. Kevin Hughes from the Massachusetts General Hospital reviewed research studies that have found that in women over the age of 70 with early stage breast cancer, radiation therapy after lumpectomy may not be necessary.  The CALGB 9343 study showed that survival rates were the same whether women received radiation therapy or not. Radiation therapy did reduce the likelihood of cancer returning in the breast (local recurrence) from about 4% in the untreated patients to about 1% in the treated patients (after 5 years of follow up). However it is important to realize that the majority of women in that study were treated with endocrine therapy, which can help reduce the risk of local recurrence. As with many decisions regarding breast cancer treatment, a careful discussion of the risks and benefits of each option is necessary.

Dr. Tina Hieken from the Mayo Clinic gave a very interesting talk on the microbiome and the impact on breast cancer. We normally co-exist with many bacteria – we have ten times the more microbial cells compared to human cells. These microbes carry out metabolic reactions that can be essential to human health. The genetic material (genome) of our microorganisms is called the microbiome. She and her colleagues studied breast tissue from women with and without breast cancer and found that the background breast microbiome is different in women with breast cancer compared to those with benign conditions. She concluded by noting that the future may involve using a microbial pattern to predict breast cancer risk, exploiting the microbiome to enhance treatment response, and that there may also be implications for a cancer prevention vaccine. The Washington Post recently covered her research – definitely worth a read for more information.

Dr. Anthony Lucci from MD Anderson discussed the “Ongoing Saga of Circulating Tumor Cells”. We would all like to see the day when a blood test can tell us with certainty if cancer has developed or returned – but we’re not there yet. After reviewing several studies evaluating both circulating tumor cells (CTC) and circulating “cell free” DNA, he concluded that this information does provide prognostic information in both metastatic and non-metastatic patients, but is not in the current ASCO or NCCN guidelines for guiding treatment. Combining the CTC status with response to preoperative chemotherapy may identify a low risk subset of patients, but noted that additional studies are needed before we can reach the ultimate goal which is improving outcomes by monitoring and responding to CTC and cell free DNA levels.

Dr. Manjeet Chadha from Mount Sinai spoke on repeat lumpectomy after prior lumpectomy and breast radiation. Traditionally, mastectomy has been recommended if cancer returns after lumpectomy and radiation therapy. On average, there is about a 10% risk of “in breast” recurrence after lumpectomy and radiation, but this will vary based on tumor and treatment type. She reviewed several studies evaluating the different types of focused or partial breast radiation that may be used in selected patients who experience recurrence of their breast cancer. She also called for additional studies in this area.

One of the last talks was by Dr. Mehra Golshan from Dana Farber. He spoke about the decision whether or not to operate on patients with breast cancer who present with Stage IV (metastatic) disease. Traditionally, we have not recommended surgery for patients with metastatic breast cancer as these patients were not expected to have long survival, and it was not felt that removal of the main tumor would impact survival. Evaluating existing studies has also been challenging because while some have shown a benefit to removal of the main tumor, the patients who underwent surgery in those studies tended to be younger and healthier. He concluded by noting that surgery in patients with Stage IV breast cancer is not standard of care, but some studies do support this practice. It is recommended that these patients be evaluated in a multidisciplinary forum and that treatment choices be individualized.

 I returned from the meeting exhausted but energized. In addition to the scientific content, the meeting is an opportunity to connect with friends and colleagues across the country. I’m already looking forward to ASBrS 2018!

This post has not been endorsed by the American Society of Breast Surgeons.

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ASBrS Issues CPM Consensus Statment

During the April 2016 meeting of the American Society of Breast Surgeons (ASBrS), a consensus conference was held to discuss contralateral prophylactic mastectomy (CPM). CPM is the removal of the healthy, opposite breast, and the rates of CPM have been increasing, for various reasons.

A patient’s decision to undergo a CPM is very difficult and is unique to each individual with breast cancer. Consensus statements and guidelines are not mandates. Rather, they are recommendations based on the best available evidence. In addition, the ASBrS statement specifically states that this document was developed to guide patient and physician discussion, and should not influence insurance coverage for the procedure.

The summary of the document states: “The consensus group agreed that CPM should be discouraged for an average risk woman with unilateral (one side) breast cancer. However, patient’s values, goals and preferences should be included to optimize shared decision making when discussing CPM. The final decision whether or not to proceed with CPM is a result of the balance between benefits and risks of CPM and patient preference”

The full statement is available online (open access) in two parts. Part 1 covers the data on CPM outcomes and risks. Part 2 discusses additional considerations and a framework for shared decision making.

Some key points noted in the manuscript include:

  • Breast conservation is preferable in appropriate patients, and neoadjuvant therapy and/or oncoplastic approaches should be considered to facilitate breast conservation
  • The risk of contralateral breast cancer (breast cancer developing in the opposite breast – CBC) in an average risk woman with breast cancer is 0.1-0.6% per year. CBC risk is higher for women diagnosed at a young age, those with a strong family history of breast cancer, and genetic mutation carriers
  • CPM does not appear to be associated with a survival benefit, with the possible exception of BRCA mutation carriers
  • CPM doubles the rate of surgical complications
  • Bilateral reconstruction may provide for improved cosmetic outcome
  • Sentinel lymph node surgery on the CPM side should not be routinely performed
  • CPM is a cost effective strategy in women with BRCA mutations. There is insufficient evidence to support cost-effectiveness in average risk women, and this is highly dependent on quality of life assumptions
  • 80-90% of women report satisfaction with their decision to undergo CPM but 20-30% of these women report post-surgical dissatisfaction with cosmesis, body image, and sexuality. Women should be counseled on the potential long term outcomes of CPM on body image and sexuality
  • CPM rates should not be used as a national quality measure
  • Additional education, resources on risks and benefits, stronger patient engagement, and enhanced decision making guidelines are needed. Shared decision making that includes a comprehensive discussion of risks and benefits is important

As I noted above, this is a difficult decision, and one that should not be made without significant education, thought, and discussion. The decision making process will likely be different for each woman. It is important that patients take their time to become educated about all of their options, and work with a treatment team who will provide you with the necessary time, educational resources, and support, to make the decision that is right for you.

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