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Updates from #SSO2019

7 April 2019

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

All of the research abstracts and posters can be found here. There were many interesting and thought-providing presentations, but it is important to remember that abstracts have not been subject to the peer-review process, and may represent incomplete data.

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

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

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Can Breast Cancer Be Treated Without Surgery?

13 March 2019

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

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

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

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

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

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

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

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

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

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

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

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

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PCP Involvement in Breast Cancer Decisions

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. 

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Updated Breast Cancer Genetic Testing Guidelines

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

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Improvement in Breast Cancer Death Rates – But Much Work Remains

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 500 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

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Breast Implant-Associated Lymphoma

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

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A Cure For Cancer by Next Year? Not So Fast…

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… 

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Decline in Cancer Deaths

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”

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SABCS 2018 Updates

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 

 

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Breast Cancer Updates from ASCO 2018

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

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