24 July 2019

This morning, the US FDA announced that it was recommending that specific models of breast implants manufactured by Allergan be removed from the market due to concerns about breast implant associated anaplastic large cell lymphoma (BIA-ALCL), a form of cancer. Allergan responded by announcing a worldwide recall of BIOCELL textured breast implants.

The FDA announcement notes that 573 cases of BIA-ALCL have been diagnosed worldwide, and the majority of the cases (481) have been linked to Allergan implants. While BIA-ALCL is thought to be curable by removing the implant and capsule, the FDA announcement reports that 33 patients have died. In 13 of the cases (of patient death) where the implant manufacturer was known, 12 patients had Allergan implants. The FDA announcement was prompted by information received since March 2019, when the FDA issued a letter to healthcare providers and held a public meeting to increase awareness of BIA-ALCL and to request that suspected cases be reported.

The plastic surgeon’s office typically keeps a record of the type of implant placed. Today’s FDA announcement stated that the majority of implants placed in the US are NOT the textured form, and that the specific type of Allergan implant implicated accounts for about 5% of all implants placed in the US. BIA-ALCL is not common, and typically presents with rapid accumulation of fluid (that a patient would notice as swelling) sometime after placement. As always, report any changes to your physician.

Update after 7/25/19 FDA call: I had the opportunity to sit in on a call with the FDA and several other surgical societies this morning and a few points were made:

  • The implants implicated in the recall were not marketed in the US prior to March 2000.
  • A small percentage of cases of BIA-ALCL have occurred in patients who have no history of textured implants.
  • Tissue expanders, the temporary “spacers” that are often used prior to stretch the skin and muscle, are often textured. They are not usually left in place for more than a few months, but the FDA did not have any information or insights as to whether these might be the cause of BIA-ALCL in patients with no history of textured implants.
  • The FDA is not recommending removal of implants in asymptomatic patients. They stressed that if implants are removed, the implant capsule (the fibrous scar tissue that normally forms after implant placement) also needs to be removed, because that is where the ALCL develops.
  • It was discussed that there is no “early detection” for BIA-ALCL, and that patients may not be comfortable with a “watch and wait” approach.
  • Concerns were raised about insurance coverage for implant removal and replacement, especially in patients who are asymptomatic. The FDA commented that insurance coverage issues are out of their scope of practice but they recognize the problem. They did note that they had met with patient advocate groups earlier today
  • All of the representatives from the surgical organizations that were on the call agreed that education of their members as well as the larger physician community is necessary. A representative from the American Society of Plastic Surgeons noted that they have been educating their members for some time and have patient resources on their website. They also stressed that if patients note any changes, they should seek out a board-certified plastic surgeon
  • Symptoms of BIA-ALCL include the sudden development of swelling (due to fluid accumulation) with or without a mass. Any changes should be promptly reported.

5 July 2019

We tend to think of most cancers as a single cell line, or clone – one normal cell develops a mutation, and that abnormal cell continues to divide. However, many tumors exhibit what is termed “heterogeneity” – meaning they are composed of cells with different genetic makeups. These cells can have different behaviors, growth patterns and response to treatment.

A study recently published in the Annals of Surgical Oncology looked at the association between tumor heterogeneity and immune cells. They found that tumors with high heterogeneity (more diverse cell population) were associated with worse overall survival. They also found that these tumors were associated with lower levels of anti-tumor T-cells (an immune system cell) and “immune checkpoint molecules”, and had a higher percentage of immunosuppressive T-cells. Their finding was noted primarily in estrogen-receptor positive (ER+) breast cancers.

Testing for different cell populations within a tumor is not routinely performed at this point in time. In addition, the authors noted that it is up for debate (and further research) which comes first – do the diverse tumor cell populations attract immune cells, or do the immune cells act to control tumor cell diversity. They noted that additional work is needed to better understand the changes that influence tumor cell heterogeneity and to develop methods to prevent it from occurring. This is just one of the reasons why a “cure” for cancer is not that simple. Cancer – even a single tumor in one patient – is not just one disease.

30 June 2019

Note – if you would like a copy of the studies discussed below but are not able to access them from the journal website, please email me: contact at drattai dot com

In a study recently published in the Annals of Surgical Oncology, Bateni et al used the National Cancer Database to assess outcomes in patients with male breast cancer based on surgical therapy. The authors found improved 10-year survival in patients who underwent breast conserving therapy (BCT) which they defined as partial mastectomy (also called lumpectomy) plus radiation therapy.

Male breast cancer makes up about 1% of all new breast cancer diagnoses; approximately 2500 men are diagnosed in the US each year. Treatment guidelines for male breast cancer are similar to those for post-menopausal women despite growing evidence that breast cancer in men is a biologically different disease versus that in women. One of the challenges for clinical trials is the relatively small numbers of male breast cancer patients diagnosed each year. However, many clinical trials have not included men. 

A total of 8445 patients with stage I and II breast cancer, treated between 2004-2014, were included for analysis. 61% underwent mastectomy, and 18% underwent BCT. 12% had mastectomy with radiation, and 8% had partial mastectomy without radiation. Median follow up was 52 months. At 10 years, overall survival was as follows:

  • 74% BCT
  • 58% mastectomy
  • 56% mastectomy with radiation
  • 56% partial mastectomy without radiation

The image below is Figure IA from the manuscript, which show the “crude” overall survival for male breast cancer patients depending on surgical therapy.

Evaluating patients who had breast conservation with or without radiation, the authors noted that patients who were older, had higher tumor stage, higher cellular grade, and triple negative histology had poorer overall survival rates. They noted that there were differences in patient age, co-morbidities (other medical conditions), margin status and chemotherapy use for patients who underwent BCT versus partial mastectomy alone. However, after accounting for these differences, survival rates still favored BCT, suggesting that radiation therapy is an important component of improved outcomes. 

Limitations of the study noted by the authors include the retrospective nature, and the inability to understand some of the factors that influenced the decision for mastectomy versus breast conservation. Her2/neu status was not uniformly reported in the NCDB until 2010, so almost half of the patients in this study did not have this information. They also noted a larger percentage (4.9 vs 1.4%) of patients in the BCT group had triple negative breast cancer, which might explain why more of these patients were also treated with chemotherapy. It is also not clear how much of an influence the use of chemotherapy and endocrine therapy had in terms of the survival rates that were noted.

In a separate article, De La Cruz et al performed a systematic literature review of the studies evaluating breast conservation in men (excluding the Bateni et al study discussed above). The authors found 8 publications meeting their criteria. Among these studies, there were 859 patients who underwent breast conservation, 14.7% of all male breast cancer surgeries in the combined papers. Reporting on the “weighted average”, local recurrence (cancer returning in the breast) was 9.9%, disease-free survival was 85.6% and 5 year survival was 84.4%. As with the retrospective database analysis, there are limitations to this type of literature review – studies may use the same data points for inclusion, including use of radiation therapy, chemotherapy, and margin status. There may be significant differences in the patient populations in the various studies reviewed. As in the Bateni et al paper, there may be multiple unknown factors that influenced a decision for surgery type.

Men tend to present with larger tumors, especially relative to breast size, so often mastectomy is recommended. However, the authors of both papers were of the opinion that breast conservation is oncologically safe and a very reasonable option for men with early stage breast cancer, if they desire. Bateni et al stressed the importance of radiation therapy if breast conservation is utilized. Both papers highlight the importance of clinical trials for male breast cancer, so that treatment recommendations can be based on the best available evidence.

Additional information on Male Breast Cancer:

4 June 2019

Encouraging news for patients with metastatic estrogen receptor-positive (ER+), Her2/neu negative breast cancer was presented at the 2019 American Society of Clinical Oncology annual meeting, and published in the New England Journal of Medicine.

The MONALEESA-7 Phase III trial evaluated the use of ribociclib in combination with endocrine therapy. Patients who received ribociclib and endocrine therapy were found to have improved overall survival rates compared to those who received endocrine therapy alone. Prior studies demonstrated improved progression free survival, but this was the first demonstration of an improvement in overall survival. Patients enrolled in this study were pre- or peri-menopausal.

Ribociclib is an oral medication belonging to the CDK 4/6 inhibitor class of targeted agents. The CDK 4/6 pathway is important for cell division. CDK 4/6 inhibitors block progression through the normal cell cycle, so cancer cells are “arrested” in a resting phase and cannot divide. This study found that at 42 months, patients treated with ribociclib had a 70% overall survival rate, compared to 46% for the patients who received endocrine therapy alone. In absolute numbers, there were 26 fewer deaths (83 or 337 versus 109 of 335) in the treatment group. Because patients who develop metastatic breast cancer after a diagnosis of early-stage disease are not re-staged, it is not possible to determine with certainty how many patients this medication may be appropriate for. Approximately 40,000 women and 500 men die from metastatic breast cancer every year. ER+ is the most common breast cancer subtype.

Prior studies have evaluated a similar drug, palbociclib, which has been approved for use in women and men with metastatic breast cancer. There are ongoing studies evaluating all 3 of the “ciclib” agents to get a better sense of whether the results will be similar across all patient populations or if a particular drug will be better for a particular subset of patients. All 3 agents are oral (pills). While side effects may be an issue for some patients, these medications are much better tolerated compared to traditional chemotherapy. Unfortunately, cost and insurance coverage may be an issue in some situations.

In addition, I do think that it is important to point out that in the current study, the majority of patients (67% in the ribociclib arm and 73% in the endocrine therapy alone arm) went on to receive other therapy – meaning that the disease progressed. We are still a long way from a “cure” despite improvements in overall survival, and we’re a long way from single-agent therapy in patients with metastatic breast cancer. Patients with metastatic breast cancer are still expected to need more than one, and in some cases multiple, agents over time as the cancer finds ways to mutate and continue to grow. The findings of this study are a step in the right direction, but much more research is needed.

Additional Information:
ASCO Post – 2019 ASCO: MONALEESA 7
NBC News – Breast Cancer Treatment Shows Hope for Younger Women

13 May 2019

Note – the survey closed on July 7th 2019. Thank you to all who participated and shared, and we will be sure to post the results when they are available!

Approximately 25-30% of patients with breast cancer who are prescribed endocrine therapy do not complete the full course of treatment, and some patients never start. Side effects of endocrine therapy are well documented but there is very little literature on the role of the medical team in helping patients manage treatment-related side effects. 

This survey is being conducted for research purposes. It is a UCLA research survey, open to women and men with a history of breast cancer who have been treated with or who have received a recommendation for endocrine therapy. 

This survey is voluntary and is completely anonymous – no identifying information, including internet protocol (IP) addresses, will be collected. The survey should take approximately 15 minutes to complete. We value your time and your opinions. 

For questions regarding this study, you may contact principal investigator Dr. Deanna Attai By phone: (818) 333-2555; by email: dattai@mednet.ucla.edu; or by mail: 191 S. Buena Vista #415, Burbank, CA 91505

UCLA Office of the Human Research Protection Program (OHRPP):
If you have questions about your rights as a research subject, or if you have concerns or suggestions and you want to talk to someone other than the researchers, you may contact the UCLA OHRPP  By phone: (310) 206-2040; by email: participants@research.ucla.edu; or by mail: Box 951406, Los Angeles, CA  90095-1406

Research Survey Link

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.

7 April 2019

The Society of Surgical Oncology held their annual meeting in San Diego, CA from March 27-30, 2019. Approximately 1700 surgical oncologists were in attendance. As the organization is geared towards the entire field of surgical oncology, only a portion of the meeting covered breast cancer. Here are some of the highlights:

Genetic Testing and Management
Dr. Judy Garber – Dana Farber
Updates in Testing and Management of BRCA Mutations
BRCA Mutation information from the National Cancer Institute
– Consider repeat testing if original genetic testing was performed prior to 2012 as more genes as well as pathogenic mutations have been discovered
– NCCN guidelines for breast cancer surveillance in BRCA 1/2 mutation carriers:
o Clinical breast exam every 6-12 months starting at age 25
o Annual MRI age 25-75 (individualize after age 75)
o Annual mammogram age 30-75 (individualize after age 75)
– NCCN guidelines for breast cancer prevention in BRCA 1/2 mutation carriers: discuss mastectomy, discuss tamoxifen
– Premenopausal BRCA mutation carriers who undergo oophorectomy experience breast cancer risk reduction. The level of breast cancer risk reduction in BRCA1 carriers is lower than in BRCA2 carriers as BRCA1-associated tumors are more likely to be triple negative
– Prenatal genetic testing is available in mutation carriers, and may be used for selective reproduction
– BRCA 1/2 mutation status does not impact breast cancer outcomes; tumor biology impact on outcomes is independent of mutation status
– BRCA 1/2 are DNA repair genes. Tumors associated with BRCA 1 tend to be triple negative and tumors associated with BRCA 2 tend to be ER/PR+, Her2- (but all combinations have been seen)
– Clinical trials are evaluating the use of cisplatin chemotherapy in patients with BRCA mutations – cancer cells are not able to repair DNA-induced chemotherapy damage due to the defective BRCA gene
– PARP inhibitors interfere with DNA repair and have traditionally been used to treat ovarian cancer. Small studies show some effect in breast cancer in the setting of BRCA mutations. Larger studies are ongoing. So far they only seem to work in breast cancer when there are BRCA mutations
– A challenge to treatment with PARP inhibitors is that there are many mechanisms of resistance, and tumors demonstrate a variable response to therapy – tests are being developed to predict response
– Lurbinectedin – a drug from sea slugs (!) may have some effect
– A very interesting comment – Dr. Garber noted that DNA breaks may be immunogenic, so there may be a role to combine PARP inhibitors and immunotherapy treatments
– Denosumab, a RANK-ligand used for bone protection in breast cancer patients, may have breast cancer risk-reducing activity – a randomized trial is pending to assess its activity as a preventative agent

Thuy Vu, Genetic Counselor – Wake Forest
What Genetic Test Should I Order?
– Once the appropriate patient for genetic testing has been identified, how to decide what lab to use? Consider lab experience, as well as cost and insurance support
– Patients with a complicated family history (multiple different cancers in scattered relatives), absent family history (adopted), and evidence of multiple cancer syndromes will benefit from NGS (next-generation sequencing) genetic panel testing
– A disadvantage of broad genetic panel testing is that there is currently incomplete information on all of the mutations that may be identified. Risk for cancers unrelated to the current diagnosis may be identified. In addition, there will be an increased prevalence of variants of uncertain significance (VUS)
– She noted to use caution when patients bring in test results from ancestry.com and similar companies – these sites often assess for SNPs (single nucleotide polymorphisms), which is not the same as testing for a genetic mutation, and full genetic testing may need to be repeated
– She acknowledged that there is a shortage of genetic counselors, even in large university centers. Many testing companies and labs now have associated genetic counselors, and there are some independent companies offering telephone counseling services

Dr. David Euhus – Johns Hopkins
ATM, CHEK2 and Other Genes
– While multiple gene mutations influencing breast cancer risk have been identified, they do not all convey the same level of risk
– As testing for multiple genes has increased, BRCA mutations are no longer the most common mutations found
– High risk genes include BRCA 1/2, TP53, PTEN, PALB2, STK11, CDH1
– Moderate risk genes include ATM, CHEK2, NBN, NF1
– These and other genes explain approximately 14-28% of genetic risk for breast cancer – most patients with a strong family history of breast cancer do not have an identifiable mutation
– There is a range of risk associated with all of the genes that in part depends on the mutation type – what type of damage does the mutation cause to the DNA. Family history of breast cancer can modify risk.
– For most of these patients, NCCN guidelines recommend annual MRI in addition to mammograms. Age to start supplemental screening depends on the mutation.
– He noted that increased screening for other associated cancers when there is no clinical benefit leads to patient harms – financial, emotional, and physical
– A good question from the floor about the role of ultrasound as supplemental screening (in addition to MRI) – Dr. Euhus states he uses 3D mammogram / tomosynthesis and does not use ultrasound unless the patient is pregnant / lactating

Dr. Kevin Hughes – Massachusetts General Hospital
What the Surgeon Needs to Know about Genetic Testing
– High cost of testing is not the problem – interpretation of the results is the challenge
– Assuming that approximately 10% of breast cancers are hereditary, over 51,000 breast cancers could have been prevented with testing
– For the breast surgeon, understanding BRCA 1/2 is not enough. There are many genes, each have different spectrum of associated cancers and associated risk; treatment needs to be individualized for the patient taking into account their specific mutation and family history
– He emphasized the point Dr. Garber made that if testing on a breast cancer survivor was performed prior to 2012, those patients should be re-tested
– Recent American Society of Breast Surgeons guidelines call for consideration of genetic testing in all breast cancer patients
– Dr. Hughes notes that this is already a standard recommendation for other cancers such as ovarian, pancreas and others
– The field is becoming more complicated – it is not expected that anyone can memorize this – go to the internet and look it up!

Resources:
ASK2ME – All Syndromes Known to Man Evaluator
ClinVar – look up specific mutations to see how they have been classified
PROMPT registry for patients with rare mutations

Breast Cancer Treatments in the Young and Elderly
Dr. Mina Sedrak – City of Hope
Treatment Strategies in Octogenarians with Early Stage, High-Risk Breast Cancer
– Incidence and mortality from breast cancer increase with age; the number of older adults in the US is increasing
– Breast cancer outcomes are often worse for older (as well as younger) women
– Older adults are underrepresented in cancer clinical trials – 1/3 of patients with breast cancer are over the age of 70, but only a small percentage of them are included in clinical trials
– Because of lack of clinical trial data in older women, patients may be under- or over-treated [DJA note – we have a similar situation in men with breast cancer].
– There is no universal definition of “old”. Aging is a continuous spectrum, and chronological age does not accurately predict functional age. The ASCO Guidelines Geriatric Assessment can help understand factors other than chronological age to predict morbidity and mortality. US Life Tables can also be used to estimate life expectancy, as well as ePrognosis. Estimation of life expectancy should be performed for all older patients before making a treatment plan
– How to best treat cancer in the elderly patient: it depends on life expectancy, aging concerns, risks / benefits of treatment and the potential impact of co-existing medical problems
– What risks can we modify and what are the patient preferences? There is no “one size fits all”

Dr. Tyler Chesney – University of Toronto
Adjuvant Radiotherapy for Older Women after Breast Conserving Surgery
– 4 randomized clinical trials addressed if elderly patients with low-risk breast cancer need radiation therapy after breast conserving therapy: NSABP B-21, A. Fyles, CALGB 9343, and PRIME II studies
o Meta-analysis of these 4 studies: 2387 patients across all trials, early stage breast cancer, hormone receptor positive. Addition of radiation therapy reduces local recurrence from 60 versus 10 / 1000 at 5 years. 2 trials had 10 year follow up, noting recurrence was 80 versus 20 / 1000 women.
o 3 of the trials provided data on axillary recurrence: absolute benefit was small, 12 versus 3 / 1000 women. No difference in distant recurrence or overall survival
– Prime I study showed that older women who underwent radiation therapy had increased fatigue over 5-10 years but similar overall health-related quality of life
– Accelerated partial breast irradiation may be an option, but some studies have shown higher local recurrence and poorer cosmetic result (depending on treatment method)
– While toxicities of radiation therapy have improved with more modern techniques, logistical concerns such as time, need to travel, and cost may be of higher concern for older women

Dr. Laura Dominici – Dana Farber Cancer Institute
Reconstruction and Body Image in Young Patients
– More than 13,000 women under the age of 40 are diagnosed with breast cancer annually in the US, approximately 7% of all new diagnoses
– Younger women newly diagnosed with breast cancer have been shown to have higher rates of anxiety and distress after diagnosis, they have historically received more aggressive treatment, and have a long survivorship period
– More aggressive surgery such as mastectomy does not lead to improved overall or breast cancer specific survival. Local recurrence is related to tumor biology, not age of the patient
– Mastectomy (single and bilateral) rates are rising, especially among younger women. Rates of reconstruction are increasing, as are rates of post mastectomy radiation
– A growing number of patients are “going flat” after mastectomy, opting for no reconstruction
– Dana Farber young women’s multicenter prospective cohort study: poorer satisfaction with breast-related, psychosocial and sexual well-being after unilateral and bilateral mastectomy. Other factors impacting poorer satisfaction include financial status, lymphedema, and the need for radiation
– 42% of women age 50 and younger (in the Dana Farber study) regret their surgical decision including primary surgery and reconstruction decision. Patients in this study were not asked what the actual regret was – doing too much or too little
– Important for patients to understand the oncologic outcomes of their decisions, and for physicians to promote shared decision making that takes into account patient preferences and concerns

Dr. Jo Chien – University of California, San Francisco
Fertility in Young Breast Cancer Patients
– 51% of women under age 40 with breast cancer are concerned about fertility; 38% desire to have future children but up to 97% are at risk of treatment related infertility. 26% report that their concerns about infertility affected their treatment decisions
– Loss of reproductive potential after cancer treatment results in worse long-term quality of life, unresolved grief / depression, reduced life satisfaction. Fertility preservation associated with less regret among young cancer survivors
– Less than 25% of general oncologists refer young breast cancer patients to fertility specialists
– Factors impacting risk of chemotherapy-induced ovarian failure: older age, baseline ovarian reserve, type of chemotherapy, and chemotherapy dose / duration
– Menses is not a surrogate marker for fertility. Fertility decline occurs ~10 years before onset of menopause. For women who remain premenopausal after chemotherapy, the majority enter menopause prematurely
– Options for fertility preservation: ovarian stimulation and cryopreservation of embryos / oocytes, GnRH agonists, and experimental techniques such as cryopreservation of ovarian tissue and immature oocyte retrieval with in vitro maturation
– Several studies have evaluated safety of letrozole-gonadotropin protocol in women with breast cancer and have found no difference in relapse-free survival. Very limited data on safety of ovarian stimulation in the neoadjuvant setting. In subset (82 patients – 34 stimulation / 48 controls) of I-SPY2 trial, no delay in start of neoadjuvant treatment and no significant difference in pCR or recurrence or mortality rates in patients who underwent ovarian stimulation before chemotherapy
– As discussed in the genetics session, Dr. Chien noted that for BRCA mutation carriers, pre-implantation genetic diagnosis is an option. Multiple follicles / embryos are required, often needing multiple stimulation cycles
– Observational studies suggest that pregnancy is safe after breast cancer.
– When is it safe to become pregnant after treatment? It comes down to patient’s underlying risk and likely their risk aversion. Dr. Chien prefers to wait to 2-3 years, but notes there is no data to support that. The POSITIVE trial is studying the impact of adjuvant endocrine therapy interruption to allow for pregnancy

Key papers
Dr. Kandace McGuire from Virginia Commonwealth University Massey Cancer Center provided an overview of 3 practice-changing papers from 2018. She noted at the start of her talk that while this is a surgical audience, all of the studies were from the medial oncology literature. This comment highlighted the multidisciplinary nature of breast cancer care – the entire treatment team needs to be aware of the latest advances and updates.

The TAILORx study assessed Oncotype Dx results and noted that many patients previously classified as intermediate risk could now be classified as low risk. Therefore, a larger percentage of patients do not need chemotherapy. However, questions remain for patients under the age of 50.

The TEXT / SOFT trials evaluated the use of ovarian suppression in premenopausal women with hormone receptor positive breast cancer. Ovarian suppression resulted in improved disease free and overall survival, but the magnitude of improvement varied according to recurrence risk. High risk patients may have 10-15% improvement. However, quality of life and fertility may be impacted by ovarian suppression in these younger women

The KATHERINE study assessed the use of TDM1 in patients with Her2/neu over-expressed tumors who did not exhibit a pathologic complete response (pCR) after neoadjuvant (before surgery) chemotherapy. Those who received adjuvant TDM1 versus trastuzumab showed an improved disease free survival, but more study is needed to assess the effect on overall survival.

Dr. V. Craig Jordan delivered the American Cancer Society / SSO Basic Science Lecture: The SERM Saga: Something From Nothing. Dr. Jordan’s presentation was a nice history lesson about the discovery and use of tamoxifen as a treatment for breast cancer.
– Dr. Jordan noted the early clues that endocrine therapy might be effective for some breast cancers – removal of the ovaries, adrenal glands, and even part of the pituitary gland led to improved outcomes (with a fair amount of associated risk)
– Tamoxifen was initially developed as a contraceptive agent, but it was not successful and was going to be discarded by the manufacturer
– The link to endometrial cancer and tamoxifen was initially denied, despite some interesting studies by Dr. Jordon noting the association. He noted that the early studies evaluating tamoxifen simply did not assess for endometrial cancer
– He noted that the cumulative frequency of uterine cancer with 2 years of tamoxifen is ~1.5%, and with 5 years of tamoxifen ~5.5%. He commented that if the studies were performed today, the data monitoring committees would “go apoplectic” over these results
– Raloxifene in early studies showed decrease in breast cancer but also decrease in bone fractures – this led to the STAR trial which assessed the ability of raloxifene and tamoxifen to reduce breast cancer development in high-risk women
– He discussed other drugs, derived from tamoxifen, that are being developed – searching for those with improved side effect profiles
– He quoted George S. Patton: “If everyone is thinking alike, then someone isn’t thinking”

Presidential Address – Serendipity and Strategy on the Path of Progress
Dr. Armando Giuliano, known to some as the “father” of the sentinel node biopsy, provided some interesting details on how his research process unfolded. He noted that “my success has been due to good luck, mixed with hard work, strategic planning, and serendipity.” Like those before him who proposed less aggressive surgical therapy for breast cancer, he was met with a fair amount of criticism. Patients and surgeons have benefited from his perseverance and dedication.

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 have not been subject to the peer-review process, and may represent incomplete data.

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

This post has not been endorsed by the Society of Surgical Oncology.

13 March 2019

A recent news article has called attention to an ongoing clinical trial, which is evaluating whether certain patients can avoid surgery for breast cancer. The article has raised many questions, so with the help of the trial principal investigator, surgical oncologist Dr. Henry Kuerer from M.D. Anderson, here is some clarification.

The most important point to stress is that currently, surgery is a necessary, “standard of care” component for the management of breast cancer. Patients interested in avoiding surgical resection of the tumor or tumor site should do so only in the context of a prospective controlled clinical trial, which has very specific eligibility requirements and other safety measures in place. 

Patients with triple negative and Her2/neu over-expressed (Her2+) breast cancers very often receive a recommendation for chemotherapy (even with no spread to the lymph nodes) due to the more aggressive nature of these tumors and improvements in survival with chemotherapy. Currently, neoadjuvant (before surgery) chemotherapy is usually used, which allows an assessment of tumor response. In about 50% of cases, no residual tumor is found in the area of surgical resection (because the chemotherapy killed all of the cancer cells) – known as a pathologic complete response (pCR). Patients and their surgeons began to ask: “If it’s all gone, why is surgery necessary?” Eligibility for the currently accruing clinical trial includes patients with triple negative or Her2+ cancers that are 5cm or smaller, with 4 or fewer involved axillary (underarm) lymph nodes.

Clinical trial participants first are treated with neoadjuvant chemotherapy. Follow up imaging after chemotherapy, including MRI, is performed. Needle biopsies (similar to those used to make the initial diagnosis) are performed at the original tumor site. If no cancer is found in these biopsy samples, the patient then undergoes a sentinel lymph node biopsy, or targeted axillary dissection (if she had originally biopsy proved axillary nodal disease). Currently, surgical removal of the sentinel / targeted nodes is necessary because it can be very challenging to perform lymph node needle biopsy after chemotherapy. If the lymph nodes are negative (“clear” / no cancer), the patients undergo radiation therapy. If there is residual disease in the lymph nodes after chemotherapy, an axillary dissection is performed prior to radiation therapy.  

A small pilot prospective clinical study at M.D. Anderson showed that utilizing image-guided biopsy in those patients who appear to have an excellent response could predict which patients in fact had residual disease in the breast with 98% accuracy – this was the basis for the current study.  Another feasibility trial, sponsored by the NRG Oncology cooperative group, in collaboration with the National Cancer Institute (NRG BR005), is ongoing.

A separate study, also performed at M.D. Anderson, was performed to address whether or not axillary surgery is required in these patients. The researchers found that when there is a pCR (including invasive and in-situ disease) after neoadjuvant chemotherapy, the likelihood of having any cancer in the axillary lymph nodes is extremely low if the patient had normal axillary lymph nodes demonstrated on ultrasound prior to beginning therapy. These patients may be able to then avoid any breast or axillary surgery.  A much larger study using the US National Cancer Database noted similar findings, but in addition, highlighted the need to perform axillary surgery in cases where there was initial biopsy-proven cancer in the lymph nodes prior to chemotherapy.

Dialing back the extent of surgical therapy for breast cancer is nothing new. Sir William Halsted died in 1922, but the extensive, disfiguring procedure bearing his name (the “Halsted radical mastectomy”) continued to be the standard of care well into the 1950-60’s. Noting that survival was not improving despite the extensive surgery, surgeons at the NSABP, led by Dr. Bernard Fisher, started to ask questions and design clinical trials. NSABP B-04 results demonstrated that there was no difference in overall survival or local recurrence whether patients underwent a radical mastectomy or a total mastectomy, and the radical mastectomy fell out of favor.

With increasing use of screening mammography, cancers were being detected in smaller sizes. Again, surgeons asked questions, and the NSABP B-06 trial was performed – this study found no difference in overall survival whether patients underwent a mastectomy with lymph node removal, a lumpectomy with lymph node removal, or a lumpectomy with lymph node removal and radiation therapy. The women who underwent lumpectomy without radiation had a higher rate of local (in the breast) recurrence (approximately 39% versus 14%), setting the standard that still holds today, for the use of radiation therapy after lumpectomy.

Less aggressive surgery for the axillary lymph nodes has also been carefully researched. Sentinel node biopsy and targeted node dissection, removing a smaller number of carefully identified lymph nodes (even in some settings where the cancer has spread into the lymph nodes) results in lower rates of lymphedema, chronic pain and arm mobility problems without impact on survival or recurrence.

Non-operative ablative therapy is also being researched, and techniques being investigated include cryoablation, as well as high frequency focused ultrasound and laser ablation.

While there may be many eyebrows raised regarding the current research (“no surgery???”), over the years it has been demonstrated through carefully constructed clinical trials that less extensive breast cancer surgery leads to similar outcomes in terms of survival and recurrence, but with lower rates of complications. Advances in the understanding of tumor biology, development of more precise targeted systemic therapy, and improvements in breast imaging and biopsy techniques have resulted in the identification of a subset of patients in whom surgery may not be required. As mentioned at the beginning of this post, this non-operative approach is currently only being offered in the context of a clinical trial, and is not yet considered standard therapy

SlideShare: History of Breast Cancer Surgery Including Landmark Clinical Trials (2015 Presentation)

19 February 2019

 A study recently published in Cancer assessed primary care physician (PCP) knowledge about breast cancer treatment decisions, and their comfort level with having treatment option discussions with their patients. 

PCPs were identified by their patients as part of a previous study. 61% of the 852 eligible PCPs responded to the survey request. Dr. Lauren Wallner and colleagues asked 4 questions:
– How frequently did the PCP discuss surgery, radiation and chemotherapy options with their patients
– How comfortable were they with these discussions
– Did they feel they had the necessary knowledge to participate in decision-making with their patients
– How confident were they in their ability to help

The survey responses indicated that 34% of the PCPs discussed surgery, 23% discussed radiation, and 22% discussed chemotherapy decisions. Those who appraised their ability to participate more positively were more likely to participate in the decision-making process. PCPs’ reporting of their participation in decision-making discussions was concordant with patients’ reporting of their PCPs’ involvement in their treatment decisions. 

While approximately one-third of PCPs reported more involvement in surgery decisions, 22% of them noted that they were not comfortable having these discussions, and 17% felt they did not have the necessary knowledge to participate in treatment decision making. Similar gaps in comfort, knowledge and confidence were seen among those who reported that they were more involved in radiation therapy and chemotherapy decisions.

The authors noted that most research to date has focused on coordinating post-treatment survivorship care between the oncology team and the PCP. However, some patients and their PCPs may desire more PCP involvement early on. As oncology specialists, we need to do a better job educating and communicating with our PCP community so that they can be more active participants and better support their patients during a very challenging time. 

12 February 2019

The American Society of Breast Surgeons has issued updated genetic testing guidelines for patients who have been diagnosed with breast cancer. The new guidelines recommend that genetic testing to include BRCA 1/2 and PALB2 mutations (and other genes as appropriate based on clinical scenario and family history) be made available to all newly diagnosed breast cancer patients. They also recommend re-evaluation and consideration of updated testing for patients tested prior to 2014.

Traditional guidelines for genetic testing have focused on age at diagnosis and family history of breast, ovarian and other cancers. However, recent studies have demonstrated that a percentage of patients who do not meet testing guidelines will be found to carry a deleterious mutation that may change surgical and other treatment recommendations. This information could also be helpful to family members who could participate in enhanced screening protocols or consider prophylactic surgery.

Not all genetic mutations are alike. Abnormalities in the BRCA 1 and 2 genes are the most common mutations associated with an increased risk of breast cancer. Mutations in other genes, such as PALB2, CHEK2, PTEN, ATM and others do not convey as high a risk. Treatment decisions in these patients needs to consider family history and other risk factors.

Another important factor to consider is that not all mutations are meaningful. Genetic testing may find a “variant of uncertain or unknown significance (VUS)” – this indicates that there is a mutation in the gene, but there is not sufficient evidence to classify it as harmful or not. Many VUS cases will be re-classified over time to reflect no impact on cancer risk. A smaller number may be re-classified as harmful.

Finally, treatment recommendations and decisions based on genetic testing status need to take into account the individual patient – their age, other medical problems, and their personal preferences.

There are currently several companies that provide comprehensive genetic testing, and costs have come down considerably. It is hoped that other national organizations, such as the National Comprehensive Cancer Network (NCCN) will update their testing guidelines, and that insurers will broaden coverage for testing. Despite some cautions, these new guidelines are an important step to help ensure that breast cancer patients, their treatment team, and their families have the information necessary to make more informed decisions.

Additional Information: Washington Post