26 April 2020

A study published in the Annals of Internal Medicine addresses the use of screening mammography in older women*. The goal of screening mammography (performed on a woman with no suspicious abnormality) is to reduce the likelihood of death from breast cancer. However, there are no randomized studies demonstrating this benefit in older women – they simply were not included in the early studies of screening mammography. Some national guidelines, including from the US Preventative Services Task Force, do not recommend screening mammography past age 75, noting that “the current evidence is insufficient to assess the balance of benefits and harms of screening mammography in women aged 75 years or older.” Some organizations, such as the American Society of Breast Surgeons and the American Cancer Society, recommend that screening mammograms continue as long as life expectancy is at least 10 years. In their Choosing Wisely statement, the American Geriatrics Society recommends that screening tests be considered in the context of life expectancy and take into account the risks of testing, overdiagnosis and overtreatment. 

This study used data from Medicare to compare death rates in women age 70 – 84 who underwent screening mammography versus those who stopped screening. Patients had no personal history of breast cancer and had a life expectancy of at least 10 years. 

There were slightly more breast cancers detected in the screening group, as expected: 5.5% in the women who underwent screening mammograms versus 3.9% in the women who did not. However, the researchers found that screening did not improve the likelihood of death from breast cancer. Among women age 70-74 there was 1 fewer breast cancer related death per 1000 women, over a period of 8 years, and this was not statistically significant. Among women age 75-84, there was no difference in breast cancer related deaths.

The authors concluded that screening mammography in older women does not significantly impact the likelihood of death from breast cancer. Limitations of this study include that it was an observational study, using information already in a database. The researchers could not adjust for certain factors including use of hormone replacement therapy, family history of breast cancer, and age at first pregnancy, which may impact breast cancer risk.  

A separate study* looked at the use of a decision aid in patients age 75 and older. The decision aid provided information about the risks and benefits of screening mammography. In this study of 546 patients, it was shown that receipt of the decision aid prior to an appointment with their physician resulted in women being more knowledgeable about screening mammography and having more discussions with their doctor about screening. In addition, 9% fewer women opted to undergo a screening mammogram. The authors concluded that the use of a decision aid may help reduce over screening in older women.

In the accompanying invited commentary, Drs. Elmore and Ngo-Metzger noted that in women age 74 with average health and life expectancy, screening mammograms prevent approximately 1 death per 1000 exams. However, 1000 women being screened can result in 79 – 96 of them experiencing a false positive (“false alarm”). They pointed out the challenges of screening mammography in older women in that the reduction in death from breast cancer can take many years, (during which the woman may die from other causes) but the potential harms are more immediate.

These two studies and the editorial raise important questions regarding the routine recommendation for screening mammography in older women. The decision whether or not to continue screening should be based on breast cancer risk as well as general health and risk of severe illness or death from other causes. When to stop screening mammography is a challenging, but important conversation to have with our older patients.

*If you are not able to access the full study and would like a copy, please email me: contact at drattai dot com

07 April 2020

Many of us are struggling to adjust to the changes we have had to make due to the COVID-19 (coronavirus disease 2019) pandemic. For those newly diagnosed with or undergoing treatment for cancer, there is an added level of anxiety and uncertainty, especially as national medical societies have made recommendations to curtail office visits, screening mammograms, breast cancer surgery and other treatments. 

It is important to understand that these guidelines and recommendations are being made in the best interest of both individual and general public health. It has become clear that people who are seemingly healthy (no cough, fever, or other symptoms of illness) may in fact carry the SARS-CoV-2 virus and may infect others. “Social distancing” and “stay at home” recommendations can help reduce the number of people infected or can at least help to “flatten the curve” – spread the number of infected out over a longer period of time, to lessen the impact on the healthcare system. 

Many breast surgeons and oncologists have transitioned to telephone and video encounters – but we are still available to see patients who need an examination or treatment. The American Society of Breast Surgeons and the American College of Radiology have issued a joint statement recommending that screening mammograms be put on hold for now. Screening studies are those performed in asymptomatic individuals – those without any lump or other concerning problem. Most facilities are still performing diagnostic imaging (workup of a problem) and biopsies. As noted in the statement, “there is no evidence that delaying screening mammography for the proposed short time period will affect mortality but there is plenty of evidence that being exposed to the coronavirus can impact mortality.”

While streets and restaurants are empty in those communities practicing “social distancing”, it’s a different story at hospitals. Although most areas in the US have not yet reached their peak incidence in terms of SARS-CoV-2 cases, many emergency departments and intensive care units are full. The healthcare system is dealing with a shortage of basic protective equipment such as masks, gowns, and gloves. In addition, medications are on backorder – medications that are needed for patients who require use of a ventilator due to critical illness are the same ones used for general anesthesia during surgery. Despite best efforts to isolate patients known to be infected, some will develop the infection while in the hospital. Surgical patients who either have or develop SARS-CoV2 infection have higher mortality rates. Physicians are becoming infected, removing them from the pool of available healthcare workers.  

Keeping one patient out of the operating room can free up personnel, equipment, and medications for someone who has become critically ill – and may be the difference between their life and death. Therefore, most hospitals have drastically cut the number of “elective” surgeries that are being performed. 

For facilities, there are 3 phases that have been described:

  • Phase I is considered the semi-urgent, or preparation phase, where hospital resources have not been exhausted, ICU beds and ventilators are available, and the number of cases in the community are not rapidly increasing
  • Phase 2 is an urgent setting, where the facility has many SARS-CoV-2 infected patients, there are limited ICU beds, ventilators and protective equipment, or the number of cases in the community are rapidly increasing
  • Phase 3 is when all hospital resources are routed to infected patients, and there are no available ICU beds ventilators, or protective equipment.

While an individual may not consider their pending surgery for cancer or risk reduction to be truly “elective”, the American College of SurgeonsAmerican Society of Breast Surgeons, and the Society of Surgical Oncology have guidelines for breast surgery that are based on the type of procedure, taking into account the situation at an individual healthcare facility or system. Most have similar recommendations:

  • Surgery for benign breast conditions and for risk reduction is not recommended at this time. This includes contralateral prophylactic mastectomy (removal of the opposite, “healthy” breast during surgery for cancer)
  • For patients with breast cancer, decisions are made based on local resources as well as the specific subtype of cancer
  • When the decision is made to proceed with surgery, it is recommended to perform the minimum possible, under local anesthesia and sedation (versus general anesthesia) if at all possible – for example some patients who desire mastectomy may be recommended to undergo lumpectomy (if technically possible) as a temporizing measure
  • Lengthy reconstructive procedures (such as autologous or “free” flaps) are not recommended by the American Society of Plastic Surgeons
  • If appropriate based on tumor biology, chemotherapy or endocrine therapy prior to surgery is recommended

These are guidelines – they are no substitute for personalized recommendations by your medical team who best know your situation as well as that of their hospital. No one takes lightly the impact of delaying surgery – both from the standpoint of treating the cancer as well as the added psychological stress on the patient and their family. However, we are dealing with a novel disease and the full impact, devastating already, has yet to be seen. While it is hoped that these restrictions will not be in place for longer than 1-2 months, many areas of the country are not expected to reach their peak SARS-CoV-2 incidence for several weeks. Please reach out to your medical team, mental health provider (if you need or have one) and each other – virtually of course – if you need help, answers or support. Stay home and stay well.

28 November 2019

A study recently published in the New England Journal of Medicine* suggests that the use of breast MRI in addition to mammograms in women with extremely dense breast can improve the rate of “interval cancer” detection.

Interval cancers are those that occur after an apparently normal mammogram, but prior to the next scheduled mammogram. An example could be a lump felt by a patient a few months after a “clear” mammogram. Interval cancers are more likely to be more aggressive (triple negative or Her2/neu over-expressed) and/or occur in women who have dense breasts on mammogram.

Researchers in the Netherlands evaluated the role of breast MRI as a supplemental screening tool in women age 50-74, who had a normal mammogram and an “extremely dense” (BIRADS 4 density) reading. After a normal mammogram, women were randomized 1:4 to supplemental MRI versus continued mammogram only (1 woman received an invitation for MRI for every 4 who continued undergoing only mammograms). The standard mammography screening in the Netherlands is every 2 years. 8061 women were in the “intent to treat” with MRI group and 32,312 in the mammogram alone group. 59% (4783) of women randomized to the MRI group actually accepted and underwent supplemental MRI.

Some of the key findings:

  • In the MRI “intent to treat” group, they found 2.5 / 1000 interval cancers and in the mammography group there were 5.0 / 1000 interval cancers
  • However, out of the 20 interval cancers discovered in the MRI “intent to treat” group, only 4 were in women who had actually undergone MRI. The other 16 were in women were randomized to the MRI group but did not have the study – they had mammograms only
  • Out of the women who underwent MRI, approximately 10% (454) were recalled for additional imaging
  • 300 women had needle biopsies due to findings on MRI, and out of those, 79 (26%) were found to have cancer. 64 of the cancers were invasive and 15 were noninvasive (DCIS). 74% of the biopsies did NOT show cancer
  • The cancers detected by MRI on average were smaller than those detected by mammography. The majority were hormone receptor positive and lymph node negative
  • DCIS was more likely to be detected in women undergoing MRI (0.31%) versus mammogram alone (0.03%)
  • 0.1% of patients who had an MRI experienced an adverse reaction including fainting, contrast (dye) reaction, and issues with the intravenous line
  • The study was NOT designed to determine if MRI improved the survival rates from the cancers detected.

Some important points were raised in the accompanying editorial by Dr. Dan Longo*. He noted that with any screening test, the goal should be that early detection of the cancer results in a higher likelihood of cure but admitted that any screening test is associated with false positives, and many patients with an abnormal test will not have cancer. He also noted that an “imprecisely defined fraction of cancers that are detected by screening do not progress to cause symptomatic disease or to kill the patient” but that “our dilemma is that for most tumors we cannot tell the difference between cancers that can kill you and those that cannot.”

The study focused on patients with extremely dense breasts, which the authors estimate account for approximately 10% of patients undergoing mammograms. It is not clear if these findings would be similar in patients with level 3 breast density (heterogeneously dense), those undergoing tomosynthesis (3D) mammograms, or in patients who are undergoing mammograms every year. They did not stratify patients by risk assessment and it’s important to note that while dense breasts are a risk factor for breast cancer, not all women with dense breasts are considered “high risk”. US national guidelines currently recommend supplemental imaging with MRI in patients who have a lifetime risk of breast cancer of 20% or greater as calculated by a risk assessment model. Due to high recall and false positive rates associated with MRI as well as possible concerns related to the contrast material, we do not currently recommend MRI for all women, or even for all women with dense breasts.

As one of their concluding statements, the authors did note that the 10% recall rate “is a concern for potential implementation of supplemental screening” [with MRI]. This study adds to the body of literature regarding cancer detection in women with dense breasts, but Dr. Longo concluded in his editorial: “… will we be putting these women at increased risk of procedures without contributing to their eventual survival?” Going forward, it will be important to look at ways to decrease false positive results and costs of supplemental imaging, as well as evaluate whether or not outcomes are improved by additional testing.

*If you are not able to access the full study and would like a copy, please email me: contact at drattai dot com

17 July 2019

There are no standard guidelines for mammographic screening for men who have no symptoms (such as a lump), even if they are considered to be at high risk for developing breast cancer. A study recently published in Breast Cancer Research and Treatment* evaluated the performance of screening mammography in asymptomatic high risk men.

The researchers reviewed a prospective institutional database at the Memorial Sloan Kettering Cancer Center, evaluating cases from 2011 – 2018. 827 men underwent mammography during that time period, but 80% were excluded from evaluation for this study as they underwent imaging due to the presence of a mass or other symptoms. Data from 163 asymptomatic patients, considered high risk due to a family and/ or personal history of breast cancer or the presence of a deleterious genetic mutation, was analyzed. 

Of the 163 men, 77% had personal history of breast cancer and 44% had a family history of breast cancer. 15% had deleterious BRCA mutations. Most of the genetic mutations (83%) were in the BRCA2 gene, as expected.

Over the 7-year time period, 806 screening mammography examinations were performed. The majority (792 studies, 98%) were BIRADS 1 or 2, indicating a normal study or benign findings. 10 (1.2%) were BIRADS 3 indicating a “probably benign” finding. Upon follow up, all of these patients were considered to have benign findings. 4 men had BIRADS 4 or 5 findings indicating suspicious or highly suspicious findings for which biopsy was recommended, and all were diagnosed with invasive ductal breast cancer.

Breast cancers in men are often diagnosed at more advanced stages than in women, and as a result, outcomes may be poorer. The authors noted that while mammographic screening has not been shown to reduce breast cancer mortality rates (the reason screening is performed) in men, the detection rate in this high-risk population (4.96 per 1000 examinations) is comparable to the breast cancer detection rate from screening mammography in average risk women. There were no false-positive (“false alarm”) biopsies in this group. The authors acknowledged one of the primary limitations of their study, the relatively small number of patients, and called for larger studies to confirm their findings. They concluded that their study “suggests that screening mammography should be performed in men at increased risk for breast cancer.”

*If you are not able to access the full study and would like a copy, please email me: contact at drattai dot com

5 July 2019

A study recently published in The Lancet Oncology found that the addition of MRI to mammography screening in high-risk patients detected breast cancers in earlier stages, but found that this technology was associated with a higher likelihood of false-positive results.

The study was performed at 12 hospitals in the Netherlands. Patients who were age 30-55 with a lifetime risk of breast cancer greater than 20% due to family history, but who tested negative for deleterious mutations in BRCA 1/2 and TP53 genes, were eligible to participate. Patients were randomized to one of the following surveillance arms:

  • Annual MRI, annual clinical breast exam, every other year mammogram [MRI-MG], or
  • Annual mammogram and annual clinical breast exam [MG]

1355 women were randomized and 231 were registered – the patients who were registered were those who did not provide consent for randomization, but followed one or the other protocol. Results from the patients who were registered but not randomized were used only in a portion of the data analysis.  

The authors found that over the 7-year study period:

  • 40 breast cancers were detected in the MRI-MG group, 15 were detected in the MG group
  • 24 invasive breast cancers were detected in the MRI-MG group, 8 were detected in the MG group
  • Invasive breast cancers detected in the MRI-MG group were smaller (9 versus 17 millimeters) than those in the MG group
  • Lymph node involvement was less likely to be seen in the MRI-MG group (4 of 24 cases, 17%) versus the MG group (5 of 8 cases, 63%)
  • There was one interval cancer (detected between screening exams) in the MRI-MG group and 2 in the MG group
  • Increased breast density was associated with higher stage at diagnosis in both study groups
  • Clinical breast exams generated a large number of false-positive results in both groups and detected only one cancer.

This study adds to the evidence nothing that the addition of MRI to screening mammography will increase the rate of cancer detection. National guidelines in the US do recommend breast MRI on an annual basis, in addition to annual mammography, for patients with a lifetime risk of 20% or greater. This study was not designed to assess outcomes for the patients who were diagnosed with breast cancer, but the authors postulated that MRI screening might lead to mortality reduction due to earlier stage at diagnosis. As reduction in mortality is the goal of screening, they stated that they plan to link the current study results with their national cancer database, and eventually publish 10-year mortality statistics for each of the groups. 

Additional Information: ASCO Post

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.

3 May 2019

The American Society of Breast Surgeons (ASBrS) has updated their screening mammography guideline, recommending that women of average risk begin annual screening mammograms at age 40. This update brings the ASBrS guideline more in line with those of the American College of Radiology and the Society of Breast Imaging, and are a departure from their previous guideline, which called for screening to start at age 45. The American Cancer Society recommends annual screening from age 45-54, followed by biennial screening with the opportunity for annual screening. The US Preventative Services Task Force recommends biennial screening starting at age 50.

The updated ASBrS guidelines recommend as a first step that all women undergo a formal risk assessment starting at age 25. Risk assessment involves using any one of a number of models to estimate 5-year and lifetime risk of breast cancer development. These models take into account age, family history, menstrual and pregnancy history as well as history of prior biopsy and racial / ethnic background. Some models take into account body mass index and breast density. The ASBrS guideline has additional recommendations, outlined below, depending on risk level. The recommendations listed for women at high risk of breast cancer are consistent with those of the American Cancer Society and National Comprehensive Cancer Network.

When to start and how often to perform screening mammography has been the subject of much debate over the years. The primary issue is the number of lives saved balanced against the harms of screening mammography. Harms include false negatives (cancer is not detected by the mammogram), false positives (suspicious areas that turn out to be benign) and recommendations for additional imaging (added cost and concerns about the potential effects of cumulative radiation). There have also been concerns raised about over-diagnosis and over-treatment: finding cancers that would never pose a threat to a woman’s health or life – but the patient is exposed to the potential harms of cancer therapy.

The goal of screening is not to detect all cancers – otherwise we would recommend complete body imaging for everyone. The goal of screening is to improve the survival from the cancers that are detected. An ideal screening test is relatively inexpensive and performs equally well in the patient population undergoing the screening. Mammography is acknowledged to be an imperfect screening tool – while relatively inexpensive and safe, it simply does not perform the same in women with breasts of different ages and densities. Approximately 1000 women need to be screened to detect 2 – 7 breast cancers, and mammography performs best in women age 50-74. In younger women, a few cancers will be detected, and there may be a survival benefit. However, because breast cancer is less common in younger women, a larger number of women need to be screened to find a single cancer, increasing the likelihood of a harm. The benefits of screening do not always outweigh the risks – at least for an individual patient.

It is also important to note that some of the new ASBrS recommendations, such as 3D mammography as the preferred type of mammogram, supplemental ultrasound in women with dense breasts, and MRI for all women with a history of breast cancer, are still undergoing investigation and are not always covered by insurance. We know that these studies will find additional cancers, but we do not yet have data on improved outcomes. My patients know that I am fond of saying “the more we look, the more we find, but not everything we find needs to be found.”

Two ongoing studies will hopefully provide additional information regarding 3D mammography and screening interval:

  • The TMIST trial is a national multi-center study assessing the performance of 3D compared to 2D digital mammography. This study will assess rates of cancer detection, callbacks and benign biopsies as well as biology of the tumors detected and outcomes.
  • The WISDOM study is evaluating a risk-based screening approach. After a comprehensive risk assessment, genetic testing, and assessment of risk tolerance, patients are assigned annual versus biennial screening. Women can self-enroll in this study (disclosure – I am not involved with the study team but I am enrolled in the study as a participant) and do not have to change mammography facility.

Until we are at a point when an individual woman’s level of risk can be accurately predicted, there is no definitive “best” screening guideline to follow. Recognizing the potential harms of screening mammography, it is no longer appropriate for physicians to simply hand out an order for an annual screening mammogram for all women starting at age 40. A balanced discussion, taking into account an individual woman’s risk and level of risk tolerance as well as the absolute potential benefits and harms of mammography is indicated. These discussions are nuanced and take time. Various genomic assays are being evaluated and it is hopeful that we will at some point have a test that can accurately predict a woman’s risk of breast cancer – which can then be used to provide more tailored guidance regarding imaging. Until that time (and I hate to end this way…), talk to your physician and medical team about what screening option is right for you.

1 April 2019

A study recently published in JAMA Internal Medicine casts doubts on the commonly held belief that addition of screening ultrasound to screening mammography improves the rate of breast cancer detection. 

It is well known that mammograms do not pick up all breast cancers. In the approximately 40% of women who undergo screening mammography who have dense breasts, mammograms may miss up to 40-50% of breast cancers. Several previously published studies have noted that supplementing mammography with screening ultrasound can detect an additional 2-5 breast cancers per 1000 scans. There is no data on whether or not the outcomes (such as survival) of these patients are improved.

The recently published study used two Breast Cancer Surveillance Consortium registries. These registries collected prospective data on screening mammography with or without same-day breast ultrasound. The data collection period was from January 2000 – December 2013. Approximately 6000 screening mammography + same-day screening ultrasounds (SM + US) in 3386 women were matched to 30,000 screening mammograms (SM) without same-day screening ultrasounds in 15,000 women. Women from the 2 registries were matched by age, year of exam, race / ethnicity, menopausal status, first degree relative with breast cancer, time since last mammogram, breast density, and prior history of a benign biopsy.

Not surprisingly, the authors found that SM + US was more often performed in women with dense breasts, in those under the age of 50, and in patients with a family history of breast cancer. Approximately 54% of the patients who underwent SM + US were considered to be “low” or “average” risk for breast cancer based on risk assessment calculations.

The breast cancer detection rate in both groups (SM + US and SM alone) was essentially identical – 5.4 vs 5.5 breast cancers detected per 1000 screening exams. Most of the breast cancers detected were invasive ductal, less than 2cm, lymph node negative, and estrogen / progesterone receptor positive.

SM + US resulted in higher false positive biopsy rates (52 versus 22 per 1000 screens) and more often a recommendation for additional, short-term follow up for “probably benign” findings (3.9% vs 1.1%) compared with SM alone.

The authors noted some limitations of their study include lack of information on the experience and expertise of the ultrasonographers, lack of information on whether or not patients underwent hand-held or automated breast ultrasound, and the possibility of misclassification of some studies, which they estimated at 4.3%.

They recommended that additional studies should be performed to more accurately identify which women will benefit from supplemental screening ultrasound. It is important to note that this is a single study, with findings contradictory to other studies, so I am not recommending that we abandon screening ultrasound based on these results. As with all other aspects of breast cancer screening, there is no “one size fits all” approach for the individual patient.

30 March 2019

The US Food and Drug Administration (FDA) recently released a statement announcing amendments to the Mammography Quality Standards Act (MQSA). The “lay person letter” that patients receive with information about their mammogram results, and aspects of mammography facility quality measures, are part of the MQSA. 

As noted in the FDA statement, proposed changes to current regulations include:

  • Requirements for uniform breast density reporting
  • Comments in the lay person letter that additional imaging may be recommended if a woman has dense breasts
  • A process to update and modernize mammography quality standards
  • Improvements in the ability of the FDA to enforce violations of standards
  • Strengthen mammogram facility record-keeping requirements to minimize loss of information

The change that most patients will notice is the requirement for breast density reporting. 

Approximately 40% of patients undergoing mammograms have dense breasts, a subjective measure of the proportion of glandular tissue (which tends to appear white, or “dense” on mammogram) versus fatty tissue (which appears darker) on mammogram. Mammograms are less sensitive in patients with dense breasts since cancers generally appear as a white lump on a mammogram, and are harder to visualize against a white dense background. In addition, patients with dense breasts appear to have a high risk of developing breast cancer – although the age at which this becomes significant is not apparent. Younger women naturally have dense breast tissue, and density tends to decrease with age, especially after menopause. Women who take estrogen hormone therapy often maintain breast density even after menopause. Genetic and individual factors also play a role – some women have dense breasts well into their 70-80s even if they are not taking hormone replacement therapy.

36 states in the US currently have breast density reporting laws, in part due to the work of Dr. Nancy Cappello. Diagnosed with advanced breast cancer after years of normal mammograms, she was informed that her prior mammograms could not identify the cancer due to “dense breasts”. Through the advocacy group that she started, Are You Dense?, she sought to change breast density reporting state-by-state. The proposed changes to the MQSA will require that all women are informed of their breast density.

While mammograms are less sensitive in women with dense breasts, they still remain an important tool for cancer detection. Calcifications and subtle areas of distortion, which can be early signs of breast cancer, may not be visualized on other imaging tests such as ultrasound or MRI. Tomosynthesis, or 3D mammography, is a form of mammography that can improve the rate of breast cancer detection and can also reduce the rate of “false alarms” or callback examinations. One recent study noted that it can identify between 2 – 5 additional cancers per 1000 exams compared to the more common 2D digital mammography. 3D mammography is not always covered by insurance.

Ultrasound and MRI are sometimes used as supplemental screening in patients with dense breasts, although practices (and insurance coverage) varies. One of the challenges is that the harder we look, the more we find – and not everything needs to be found. False positive findings (false alarms) may result in unnecessary biopsies or increased imaging for a period of time to confirm that the finding is not cancer. MRI (as currently performed) requires the use of the intravenous contrast material gadolinium, which in one form (not the form most commonly used for breast MRI) has been linked to deposits in the brain and kidneys. MRI is most commonly recommended as supplemental screening for women considered to be in a high-risk category.

The proposed FDA changes to MQSA are a welcome update. There is a lot of work to be done towards the goal of personalized breast cancer screening based on risk. However, standardization of the notification process and increased oversight of mammography facilities are important steps.

Additional Information: NBC / Today Show – FDA Wants Women to Know About Breast Density

11 March 2019

A study recently published in JAMA Oncology adds to the growing body of literature noting the advantages of digital breast tomosynthesis (DBT), also known as 3D mammography, compared to the more widely available digital (2D) mammography (DM).

While mammography is still considered the “gold standard” for breast cancer screening, there are some limitations. Approximately 40% of women have dense breasts by mammography, and cancers are not seen as easily in these patients. In addition, overlapping areas of glandular tissue can masquerade as concerning findings on screening mammograms, so some women are “called back” for additional views. The additional diagnostic studies attempt to determine if the abnormality is indeed a lump, or if it is simply lumpy tissue or other benign findings.

In the current study, Dr. Conant and colleagues performed an analysis of patients within the PROSPR (Population-based Research Optimization Screening through Personalized Regimens) consortium. They included women age 45-74, without a known history of breast cancer, who underwent screening mammography at 3 research centers using DM and DBT between 2011 – 2014. The researchers evaluated recall / callback rates and in women who had at least one year follow up, they assessed biopsy and cancer detection rates. There were 101,000 patients in the DM group and 24,900 patients in the DBT group.

The researchers found that across all age groups the recall rate was lower and the cancer detection rate was higher in the DBT group. This was true even in the women age 40-49, whether they had dense or non-dense breasts. In this group of younger women, the detection rate with DBT was 1.7 per 1000 examinations higher compared with DM in the setting of non-dense breast, and 2.27 / 1000 higher in dense breasts. They also noted that DBT was associated with a higher likelihood of detecting smaller cancers with negative lymph nodes.

Some limitations of the study include: incomplete data on risk assessment, non-randomized sample resulting in slight differences in risk profile, and relatively small number of cancers detected. However, in an accompanying commentary, Drs. Bahl and Lehman suggested that as DBT did find more cancers in younger women, guidelines for routine breast screening with DBT for women age 40-49 (some guidelines recommend starting at age 50) should be reconsidered. 

Screening mammography in younger women does detect (some) breast cancers, and this and other studies show that a few more will be detected with DBT versus DM. The intense debate around screening mammography in women younger than 50 revolves around the smaller number of cancers in women in this age group (compared to over 50) and conflicting survival data – early detection does not always result in improved outcomes. The goal of any screening test is to improve survival, and Drs. Bahl and Lehman noted that none of the current DBT literature addresses clinical outcomes –  rather, it focuses on metrics such as cancer detection and recall rates. They noted that at this point in time, large trials assessing survival benefit from screening mammography may not be practical. 

Drs. Bahl and Lehman note that more studies are needed, and they comment on the TMIST trial – this is a large ongoing multicenter trial evaluating DBT and DM in women age 45-74. The TMIST study will evaluate cancer detection and recall rates, and will compare the number of advanced cancers in each group. Drs. Bahl and Lehman also noted that more research is needed to determine whether there is an added benefit of utilizing supplemental screening ultrasound in women with dense breasts who undergo screening with DBT versus DM.

There are a few additional points regarding DBT to be aware of. DBT is associated with a slightly higher radiation dose compared to DM. This type of mammogram does still involve breast compression, although many women note it is not as tight as standard mammography. In addition, DBT is not always covered by insurance, and facilities vary tremendously in their charges – some do not charge at all if insurance does not cover (only billing for the standard DM), and I’ve seen charges up to $150 or more. In addition, the harder we look, the more we find, and DBT does pick up some findings that result in biopsy and even surgery that turn out to be benign. However, it seems that as radiologists in a particular facility become more comfortable with DBT the false positive (“false alarm”) rates decrease.

The TMIST study will hopefully provide more guidance for patients and their physicians. In the meantime, if DBT is available in your area and you have dense breasts, it is reasonable to discuss this newer technology with your physician to see if it is right for you.