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

11 February 2019

Half a million breast cancer deaths averted! That’s certainly a headline that will get attention. A study just published in Cancer concluded that approximately 500 million deaths from breast cancer among women in the United States (US) have been averted over the past 30 years due to screening mammography and improved therapy.

The most important point to understand about this study is that it did NOT look at every woman who was diagnosed with breast cancer since 1989 and tabulate deaths in these women – there is no such repository of data that captures every single diagnosis and death from cancer. The study was based on database analysis as well as modeling and extrapolation.

This study utilized data from the National Cancer Institute’s Surveillance Epidemiology End Results (SEER) program – which collects data on cancer diagnosis, treatment and survival for approximately 30% of the US population. Different states and counties have been added over the years to help ensure that the database reflects the racial, ethnic and socioeconomic diversity of the US. Data points are added to reflect current scientific knowledge and changes to staging systems. Current year reported numbers are estimates, as data entry and analysis lags several years. This article provides a history of the program and discusses some of the limitations.

For this study, the authors analyzed breast cancer mortality data from 1989 for women age 40-84. They concluded that cumulative breast cancer deaths averted over the past 30 years ranged from 384,000 – 614,500.

The most recent data in the SEER registry for US breast cancer incidence and deaths extends through 2015. Therefore, information from 2016 – 2018 is based on estimates and projections. They utilized 4 different models to estimate “background breast cancer mortality rates” – the likelihood of death from breast cancer without screening mammography or modern therapy. These 4 models use different assumptions about breast cancer mortality rates based on trends prior to 1989, resulting in a range in the estimated number of lives saved. The authors combined this information with US population data obtained from census reports and estimates. The authors noted that they made no attempt to separate out the effect of screening mammography versus treatment, and also noted that the SEER database did not include information on whether newly diagnosed breast cancer patients had undergone a mammogram within 1-2 years of diagnosis. In addition, they commented that only about 50% of women age 40 and over in the US undergo screening mammography every or every other year.

One of the authors, Dr. Hendrick, commented in the press release that accompanied the article that “The best possible long-term effect of our findings would be to help women recognize that early detection and modern, personalized breast cancer treatment saves lives and to encourage more women to get screened annually starting at age 40.” [emphasis mine] However, as the authors did not separate out the effect of screening mammography versus modern therapy on breast cancer mortality, the highlighted part of his conclusion does not seem to be supported by the results of this study.

Studies such as these often raise more questions than they answer. 500,000 lives saved over 30 years sounds like tremendous progress – but we know that in the US, approximately 40,000 women and 2500 men die every year due to metastatic breast cancer. A lot of the disconnect is that studies like these often report death rates, usually per 100,000 people, not absolute numbers. Treatments have improved, and screening mammography has made a difference. But as the US population is growing and aging (and the likelihood of breast cancer increases with age) there may be more individuals with breast cancer. Cancer incidence also increases with increased use of screening mammography (due to increased detection), but not all of these cancers are lethal. Rates of death from breast cancer decrease, but absolute numbers may not.

I bring up these last points not to put a damper on some of the glowing headlines regarding this study, but to ensure that we don’t lose focus regarding the work to be done. Approximately 40,000 women and 2500 men will die this year due to metastatic breast cancer. We’ve made tremendous progress, but it’s not time to celebrate just yet.

The referenced article in Cancer is behind a paywall. If anyone would like a full copy, please email me: contact at drattai dot com

6 February 2019

The US FDA just issued a letter to healthcare providers, to increase awareness of breast implant associated anaplastic large cell lymphoma (BIA-ALCL).

BIA-ALCL is a rare type of T-cell lymphoma, not a type of breast cancer. Approximately 457 cases have been reported and there have been 9 associated deaths. It is estimated that approximately 1.5 million implants are placed per year, worldwide.

Most cases of BIA-ALCL have been in patients with textured implants, although it has been reported in association with smooth implants as well. The current FDA letter notes that many of the reports they have received do not include the surface texture of the implants.

Research has focused on the role of chronic inflammation and perhaps ongoing low-grade infection as potential causes. BIA-ALCL typically presents several years after implant placement, usually as a seroma (fluid) around the implant or as a mass in the implant. Treatment includes removal of the implant and associated capsule (fibrous “shell” that forms around the implant). This is often curative, although some patients may require chemotherapy or radiation. Prognosis appears to be very good. 

In December 2018, Allergan, one of the implant manufacturing companies, suspended European sales of specific types of textured implants to comply with a recall notice for textured implants when their product certification expired. Currently, there is no recall recommendation in the US.

The FDA communication stressed that the number of cases is extremely low relative to how many implants are placed and is not currently recommending that women have their breast implants removed. They are recommending that all cases be reported both to the FDA and to the American Society of Plastic Surgeons PROFILE registry.

On January 28th (before today’s letter to providers was released) FDA Commissioner Dr. Scott Gottlieb announced that an FDA public meeting will be held in late March to discuss concerns related to breast implants. A recent study has noted possible associations with autoimmune disease, BIA-ALCL as well as general safety issues – these will likely all be discussed. Dr. Gottlieb has noted that additional information including a link for public comments will be posted 15 days ahead of the March 25-26 2019 meeting.

 

Additional Information:
Insider: FDA Warns About Cancer Linked to Breast Implants
AP: FDA Alerts Doctors of Rare Cancer with Breast Implants

30 January 2019

The buzz this morning came from a group of scientists in Israel, claiming that they have developed a cure for cancer – one that will work on ALL cancers – and it will be ready for patient care within a year. Amazing!!

But not so fast. The report, which first appeared in the Jerusalem Post, and then was picked up by multiple news outlets, described research that has only been carried out in mice. The article quotes the researchers: “the company has concluded its first exploratory mice experiment…” and then goes on to state: “Our results are consistent and repeatable.” The article read as a press release, and there was no link to any published research.

I am not a basic science researcher, so for a deep dive on the science please review Dr. David Gorski’s post. An important point that he highlighted – the research findings have not been published a peer-reviewed journal. Dr. Matthew Hall, who is the biology group leader for the National Center for Advancing Translational Sciences at the NIH, posted this thread on his twitter feed:


Dr. Hillary Stires, a breast cancer researcher at Georgetown, noted:

Many new drugs are first tested in mice. Dr. Susan Love notes that mice do not naturally develop breast cancer. Researchers inject tumor cells into the mice in order to then study the responses to treatment. Just because it works in a mouse does not mean it will work in a person!

 

We all want a cure for cancer. Yes – even the surgeons, oncologists and researchers. We will find something else to do if this disease is cured. But cancer is not one disease and the concept of “The Cure” that will work for all cancers is probably not realistic. Articles such as this, and the avalanche of coverage that followed, only raise false hope among patients and their loved ones.

The Modern Tragedy of Fake Cancer Cures
Scientists Say They’ll Have a Cure for Cancer Within a Year
American Cancer Society / Dr. Lichtenfeld Blog
If It Sounds Too Good To Be True… 

9 January 2019

The American Cancer Society has just published their updated “Cancer Facts and Figures”, documenting cancer incidence and mortality rates. When combined by disease site, cancer death rates have decreased by 27% from 1991-2016, resulting in approximately 2.6 million cancer deaths avoided. From 2007 – 2016, cancer death rates have declined approximately 1.8% per year for men, and 1.4% per year for women. From 2006 – 2015, rates of cancer development increased approximately 2% per year for men and were stable for women.  It is anticipated that there will still be more than 1.7 million new cancers diagnosed and 600,000 cancer-related deaths in 2019.

The most common cancers in men are lung, prostate and colorectal, and the most common cancers in women are breast, lung and colorectal. Breast cancer accounts for 30% of all new cancer diagnoses in women.

Lung cancer is the most frequent cause of cancer-related deaths in both men and women. Much of the decline in incidence and mortality is attributed to a decline in smoking rates, but it important to note that many cases of lung cancer occur in non-smokers. Rates of new lung cancer cases have decreased by 3% per year in men and 1.5% per year in women, and these differences are not fully explained by smoking rates – especially in cases of lung cancer in younger women. In addition, while lung cancer related deaths in men decreased by 48%, women only experienced a 23% reduction in death rates. 

Improvements in screening and treatment have resulted in a decreased number of deaths due to lung, breast colorectal and prostate cancer, and breast cancer death rates decreased approximately 40% from 1989 – 2016. However, there has been a modest increase in breast cancer incidence, in part due to the association of breast cancer development with post-menopausal obesity as well as alcohol intake. 

While the prostate cancer death rate has decreased, there has been some flattening of the curve from 2013-2016. This may be related to more recent guidelines that do not recommend routine testing of the prostate-specific antigen (PSA) in patients without symptoms.

Colorectal cancer death rates declined 53% from 1970 – 2016, but in patients younger than age 55, new cases of colorectal cancer have increased almost 2% per year since the mid 1990s

Death rates in cancers related to obesity, including pancreatic and uterine cancer, have been increasing. Deaths due to liver cancer have also risen, with an increasing number of cases related to obesity rather than alcohol and chronic hepatitis.

There has been a decline in the racial gaps in mortality rates, but blacks are still 14% more likely to die of cancer compared to whites (33% 25 years ago). While this is encouraging, the economic gap is growing, especially related to cancers that have seen improvements due to early screening and treatment, improved nutrition and smoking cessation.

It was noted that cancer risk increases with age, and those over 85 account for approximately 8% of all new cancer diagnoses. Cancer is also noted to be the 2ndleading cause of death, after heart disease in this population. There may be many challenges to diagnosis and treatment in older adults due to the presence of co-existing medical conditions as well as other factors. 

It is important to note some limitations of the report. Information is gathered from several sources and data may be incomplete. The current report notes incidence rates through 2014 and survival data through 2015. 

The general downward trend in cancer incidence and improvement in survival is encouraging, but there is much work to be done.

Additional Information:
KPCC Air Talk interview with Dr. Attai
American Cancer Society Press Release
American Cancer Society “Facts and Figures”

12 December 2018

The San Antonio Breast Cancer Symposium is the largest medical conference devoted to breast cancer. Held every year in San Antonio, TX, it attracts a large international audience and there are often practice-changing studies. While I was not able to attend the meeting in person, I’ve provided just a few of the studies that caught my attention. This is by no means a comprehensive post – the meeting is enormous – but I have also included several summary links below with additional information.

Her2/neu Positive Breast Cancer
The KATHERINE study assessed patients treated with chemotherapy and trastuzumab (Herceptin) prior to surgery. Patients who had residual disease at surgery (meaning the chemotherapy did not kill all of the cancer) were then treated either with trastuzumab (standard of care is to complete 52 weeks of therapy) or trastuzumab-emtansine (T-DM1, Kadcyla). The study found that after 3 years of follow up, patients treated postoperatively with trastuzumab emtansine had a 50% lower risk of developing recurrence of invasive breast cancer (12.2% versus 22.2%). The findings were published on the day of presentation in the New England Journal of Medicine.

Adverse events were more common in the trastuzumab-emtansine arm (98% versus 93%). 25.7% had grade 3 or higher adverse events in the trastuzumab-emtansine arm compared to 15.4% in the trastuzumab arm. While based on these results, there is some anticipation of FDA approval, cost of the medication and insurance coverage are significant concerns.

Relationship Between pCR and Outcomes
Patients who receive neoadjuvant (prior to surgery) chemotherapy and are found to have no residual tumor (pathologic complete response – pCR) at the time of surgery, had improvements in recurrence and survival rates. The meta-analysis showed that approximately 21% of treated patients had a pCR, which was more likely if the tumor was triple negative or Her2/neu positive. The event-free survival rate was 88% in patients who had a pCR versus 67% for those with residual disease. The authors noted that in patients who had a pCR, additional chemotherapy after surgery may not be necessary. In addition, they suggested that in whose  who had residual cancer, additional chemotherapy (see the KATHERINE study above) could be considered.
ASCO Post on pCR Meta-Analysis

Tamoxifen for DCIS, LCIS and ADH
Tamoxifen is often used to help reduce the risk of developing invasive breast cancer in patients who are at high risk, including those with ductal carcinoma in-situ (DCIS), lobular carcinoma in-situ (LCIS) and atypical ductal hyperplasia (ADH). The standard dose of tamoxifen is 20mg daily. Hot flashes and sleep disturbance impact some patients who take tamoxifen, and the medication is also associated with a risk of developing blood clots and endometrial cancer. These potential side effects keep some women from even starting the medication. In addition, studies note that approximately 25-30% of breast cancer patients treated with endocrine therapy stop treatment due to side effects.

The TAM-01 study compared a low dose of tamoxifen (5mg per day) to placebo in patients with DCIS, LCIS and ALH. 500 patients were randomized and treated for 3 years. After median follow up of 5 years, 5.5% of patients in the low dose tamoxifen arm and 11.3% of patients in the placebo arm had recurrence or development of new disease, suggesting a risk reduction of approximately 50%. This is what is also seen from the standard, 20mg dose. Side effects were similar in the 2 groups.

The findings suggest that a very low dose, 3 year (current standard is 5 years for risk reduction) of tamoxifen may be sufficient in these patients who are on the medication for risk reduction. Unfortunately, the results cannot be extrapolated to patients who are on tamoxifen as part of treatment for invasive breast cancer. It was also noted in some of the commentary that tamoxifen is not commercially available in 5mg doses, but patients may consider taking 10mg every other day.
ASCO Post on TAM-01

Genetic Testing
Genetic testing in patients diagnosed with breast cancer is based on age at diagnosis and family history of breast, ovarian and other cancers. A study presented and simultaneously published in the Journal of Clinical Oncology noted that approximately 50% of patients with a pathogenic or likely pathogenic mutation were missed by current testing guidelines. Of patients who did not meet current guidelines for genetic testing, 7.9% were found to have a pathogenic or likely pathogenic mutation. The authors recommended panel genetic testing for all newly diagnosed breast cancer patients, which certainly could impact treatment recommendations surveillance and treatment recommendations for family members.

Hot Flashes
Oxybutynin (Ditropan and others) is a medication commonly used for urinary incontinence. It was compared to placebo in a double-blinded study, to assess impact on menopausal symptoms in women being treated for breast cancer with tamoxifen or aromatase inhibitors. The study showed that patients taking oxybutynin had decreased hot flash scores and also reported improvements in sleep and quality of life.
ASCO Post interview with Dr. Leon-Ferre

Radiation Therapy after Lumpectomy
The long-awaited results of NSABP B-39 were presented by Dr. Frank Vicini. There are several ways to deliver radiation therapy after lumpectomy – traditional whole-breast irradiation and various forms of partial breast irradiation (external- and catheter-based). The study noted that after 10 years of follow up, local (in-breast) recurrence rates were low in all groups, approximately 4%. Patients treated with partial breast irradiation had a slightly higher (<1%) rate of in-breast recurrence. This study is important for 2 reasons:
– Local recurrence rates were very low, approximately 4%. We have traditionally quoted (based on older studies) a local recurrence rate of approximately 10% after lumpectomy and radiation. This current study notes that local recurrence rates after lumpectomy and radiation are very close to that of mastectomy (1-5%).
– Partial breast irradiation is a reasonable option for selected patients. There was a small (but statistically significant) increase in local recurrence compared to whole breast radiation. Whether that difference is important for an individual patient or not is something that should be discussed with her treatment team. The study noted no difference I overall survival. Grade 3 and 4-5 toxicities were slightly higher in the patients who received partial breast irradiation compared to whole breast irradiation (9.6% versus 7.1% grade 3 and 0.5% versus 0.3% grade 4-5).

It is important to note that at the time of study accrual, whole breast irradiation was given over the course of approximately 6 weeks. Current practice is to utilized a “hypofractionated” protocol, which treats in about 3 – 3 ½ weeks.  

Breast Surgery Choice and Quality of Life
A study assessing long-term quality of life in young patients with breast cancer found that those who underwent unilateral or bilateral mastectomy had lower breast satisfaction and sexual / psychosocial well-being scores compared to those who underwent breast conserving surgery. 561 patients were enrolled with a median age at diagnosis of 37. 28% underwent breast conserving surgery, and 72% underwent mastectomy. 72% of the mastectomy patients had a bilateral procedure. Assessments were performed using the BREAST-Q questionnaire, which is a validated survey tool. Patients were surveyed a median of 5.8 years after treatment.

While the results were presented in abstract (not full peer-reviewed manuscript) form, it is still important to consider this information either as a physician counseling a patient on her options or as a patient deciding on her treatment options.
ASCO Post interview with Dr. Dominici

Other Resources:
SABCS Abstracts
ASCO Post Symposium Updates

AACR Blog
Oncology Times – Dr. George Sledge
OncLive Podcast

This post has not been endorsed by the San Antonio Breast Cancer Symposium 

 

14 August 2018

I was honored to participate in a Sharsheret national webinar, where breast cancer research that had been presented at the June 2018 meeting of the American Society of Clinical Oncology was reviewed. The webinar video and transcript are linked below. Dr. Sharyn Lewin, a gynecologic oncologist, presented ovarian cancer research updates.

Transcript Link

Additional Sharsheret Symposia Transcripts

This post has not been endorsed by the American Society of Clinical Oncology

24 June 2018

Two studies have recently been published which discuss patient reported outcomes and complication rates after post-mastectomy reconstruction surgery.

First a bit of background information on post-mastectomy reconstruction. The most commonly performed type of reconstruction utilizes implants. Often, a temporary tissue expander (TE) is placed by the plastic surgeon at the time of mastectomy. The TE is gradually “inflated” over time (using saline / salt water solution). When it gets to the desired size, a second operation is performed to exchange the TE for the implant. The TE and expansion process are necessary because after a mastectomy, the skin is thinned out (from removal of the breast tissue) and placement of the larger implant could compromise the blood supply to the skin and the healing process. However, a small percentage of patients are candidates for “direct to implant” reconstruction, which bypasses the TE step.

After mastectomy and implant reconstruction, patients usually spend 1-2 days in the hospital. The implants typically are placed below the pectoral (chest wall) muscle, which may result in pain and muscle spasm during the recovery period. A small percentage of patients may be candidates for “over the muscle” implant reconstruction. Implants may be filled with saline or silicone gel. Implants are foreign objects and are not meant to last forever – they may leak or may need to be replaced for other reasons. The FDA currently recommends that MRI be performed 3 years after silicone implant placement and then every other year to assess for “silent rupture” of silicone implants. However, insurance does not always cover these implant surveillance MRI scans. Potential complications of implant surgery include capsular contracture and infection which may require implant removal. Some women are bothered by the firm nature of some implants, or “rippling” which may be visible under the skin. Implants have recently been associated with a rare form of cancer – anaplastic large cell lymphoma. Routine mammogram, ultrasound or MRI are not generally recommended for breast cancer surveillance in patients who undergo mastectomy and implant reconstruction.

Autologous reconstruction (AR) utilizes the body’s own tissue. The TRAM (transverse rectus abdominus myocutaneous) flap was previously the most common type of AR. During the TRAM procedure, an incision is made in the lower portion of the abdomen (similar to a “tummy tuck” procedure) and the rectus muscle (responsible for “six-pack abs” in athletes) is removed with the overlying skin. That muscle and skin is then used to reconstruct the breast. The latissimus flap utilizes muscle and skin from the upper back. TRAM and latissimus flaps are generally performed as “pedicle” flaps – meaning their original blood supply stays intact.

With improvement in microvascular techniques, there has been an increase in the use of “free flaps” – this means that the original blood supply of the tissue for reconstruction is disconnected from its origin, and the blood vessels from the flap are sutured into blood vessels in the chest area. This has allowed the use of fat only for reconstruction, sparing the muscle. The most commonly utilized free flap is the DIEP (deep inferior epigastric perforator) flap. Other free flaps use fat from the thigh or buttock area.

AR surgeries are much longer – free flap procedures they may take up to 8-10 hours. Most patients are hospitalized for 4-5 days, including 1-2 days in the intensive care unit to monitor the blood supply to the flap. The recovery may be longer than implant reconstruction surgeries since healing needs to take place both in the chest area and in the abdomen (or thigh or buttock depending on the type of flap). The overall cosmetic result is generally more natural looking in patients undergoing AR. In patients having only one breast removed, it is much easier to “match” using AR techniques. The flap reconstruction also tends to feel much softer compared to implants (since it is the patient’s own fat) – but usually there is no sensation in the skin (or nipple if preserved) after mastectomy regardless of the type of reconstruction. The use of mammogram, ultrasound or MRI for surveillance in AR patients is controversial and practice varies considerably.

The 2 JAMA Surgery studies evaluated patient reported outcomes and complication rates after both implant and AR surgeries. The majority of patients were followed for 2 years. Overall, there were complications in 32.9% of patients – this includes everything from a minor skin infection treated with oral antibiotics to more serious complications including repeat surgery and reconstruction failure. 19.3% of patients required a repeat operation. 5.4% of patients had a failed reconstruction, where the implant or AR needed to be removed. At 2 years, patients undergoing AR had higher rates of complications including re-operations compared to patients who underwent implant reconstruction, although implant reconstruction procedures had higher rates of failure. Infections were also higher in implant reconstruction patients. In these studies, follow up only averaged 2 years – with longer follow up, patients with implant reconstruction may be found to have higher rates of complications since capsular contracture and implant leakage tend to develop over a longer period of time. Radiation during or after reconstruction, chemotherapy during or after reconstruction, and bilateral surgery were factors associated with higher complication rates in both groups of patients.

In evaluating patient reported outcomes, the authors noted that patients who underwent AR surgeries had higher rates of satisfaction with the reconstructed breast, physical well being of the chest, psychosocial well being, and sexual well being compared with those who underwent implant reconstruction. The AR patients did report lower measures of abdominal physical well being compared to implant reconstruction patients. Follow up in this study was also about 2 years for the majority of patients –  only 21% of patients returned the survey at 3 years and 10.2% of participants returned the survey at 4 years. It is unclear if the implant reconstruction patients might report higher satisfaction levels if surveyed at a later point in time. The authors noted that due to the smaller number of patients who completed surveys at 3 and 4 years, conclusions in these groups of patients could be influenced by selection bias. Essentially that means that the small group may not be representative of the whole study population – for example, patients who are doing well might not be motivated to complete a lengthy survey compared to a patient who is having problems.

These findings should stress to patients that reconstruction is a “process not a procedure” – these are major operations with the potential for short and long term complications. I think that these 2 studies will contribute to how we discuss surgical options and potential complications with our patients, but the results may not make the decision-making process easier for patients. Patients trying to make a decision about surgery have already been told they have cancer – that alone is enough to shake even the strongest of clear thinkers. I have not figured out how to ensure that a patient is making a truly informed decision in this situation except through repeated discussion and questioning. As physicians we have made progress in helping our patients make decisions based on education and not fear. But is a truly informed decision even possible when the overriding reason for the decision is a potentially life threatening condition? I’m not so sure.

New York Times – One in Three Women Undergoing Breast Reconstruction Have Complications

 

4 June 2018

The American Society of Clinical Oncology (ASCO) annual meeting, a gathering of over 40,000 oncology specialists, was held this past weekend in Chicago. One of the studies that received a significant amount of press attention was the TAILORx study.

There are several genomic tests which evaluate a tumor’s DNA to better determine how aggressive that tumor is, and how likely it is to recur without chemotherapy. The Oncotype Dx test was the first commercially available one. A sample of tumor is sent for analysis and the result is reported as a “score” which is then assigned to one of 3 categories – low, intermediate and high risk of recurrence. A sample of the report generated from the test is shown below. It is important to note that the Oncotype Dx test was validated in patients who received endocrine therapy, so the results assume treatment with tamoxifen or an aromatase inhibitor. It is appropriately used in patients with Stage I or II breast cancer, with spread to 1-3 underarm lymph nodes, if the tumors are estrogen receptor positive (ER+) and Her2/neu negative (Her2-). The results of the low risk cohort were published in 2015, which confirmed that patients with low scores receive little benefit from chemotherapy.

Sample Oncotype Dx Report

The study presented at ASCO reported on the results of the intermediate risk group. For the purposes of the study, intermediate risk was defined as a score of 11-26. It is important to note that in patients outside of the study, intermediate risk is a score of 18-31. However, as patients in the lowest risk category did not receive chemotherapy as part of this study, the categories were shifted to the left to be more cautious. Patients enrolled in the study were women between the ages of 18-75, with a median age of 55-58. Eligibility criteria included patients who had tumors smaller than 5 cm, ER+, Her2-, and with negative underarm lymph nodes (as determined by surgical pathology – all patients in this study underwent surgery). Patients with an Oncotype Dx score of 11-26 (69% of the total study population, about 6700 patients) were then randomized to chemotherapy followed by endocrine therapy, or endocrine therapy alone. Median follow up was 7.5 years.

The study showed that there was no significant difference in the overall survival (~94%), invasive cancer disease free survival (~84%) or distant disease free survival (~95%) between the 2 groups. However, in women under the age of 50, it was found that those with scores of 16-25 did receive some benefit from chemotherapy. It is unclear from the study if the benefit in these patients was specifically from the chemotherapy, or if it was that menstrual cycles and ovarian function are suppressed with chemotherapy, which then lowers estrogen levels. The authors raised the question of whether or not similar results in this group of patients could be achieved using medications to suppress the ovaries (which would induce menopause) and an aromatase inhibitor instead of chemotherapy.

It is important to note that a low risk score does not mean the patient will not develop a recurrence or metastatic disease – it simply means that the risk of recurrence is extremely low and that chemotherapy will not significantly improve on that low risk. It is also important to keep in mind that this study did not include patients with triple negative or Her2/neu positive breast cancer, or patients where the cancer had spread to the lymph nodes.

There are several commercially available genomic tests, and which test is used for a particular patient is often related to guideline recommendations and physician preference. Most of these tests are covered by insurance but the costs are high (~$4500.00) and patients should check with their insurance to determine if they have a share of cost. Most of the testing companies have payment assistance programs. For patients right on the edge of one of the risk categories, treatment decisions are not always as clear cut, and should be made in the context of the patient’s other disease factors and as part of a balanced discussion of the risks and benefits of treatment as well as patient preferences.

There has been a lot of focus on de-escalaton of therapy, and rightly so. While chemotherapy and other toxic treatments have their place, there are significant short term and long term side effects, so determining which patients have the best likelihood of benefit from these treatments is important. Not all cancers will respond to chemotherapy, and in those cases, the patient is subjected to all of the harms and receives none of the benefit.

Additional information from the ASCO Post