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

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

14 January 2019

The article discussed below is behind a paywall. If anyone would like to receive a full copy, please email me: contact at drattai dot com and I will be happy to share.

The National Coalition for Cancer Survivorship (founded by a physician who was treated for cancer), the National Cancer Institute, and the American Cancer Society consider someone to be a cancer survivor from the time of diagnosis until death. 

Of course, one size never fits all, and many patients do not consider themselves to be cancer survivors for various reasons. Patients are aware that cancer can recur even many years after treatment. Those with metastatic disease are aware that they will likely die due to the cancer. Some find the term survivor as well as any attempt at “labeling” to be offensive, not wanting to be defined by their cancer. However, some patients and their families do identify by the term, proud of the fact that they indeed survived the ordeal of cancer treatment.

In order to gain an understanding as to how patients treated for cancer prefer to be identified, researchers tapped into a large online patient community focused on breast cancer research, the Army of Women. The authors received approximately 1400 responses to their survey. Those who were undergoing treatment were less likely to identify with the term cancer survivor compared to those who had completed therapy. Those with metastatic disease and older patients also felt less positive about the term. Open-ended questions noted approximately 60% negative, 30% positive and 10% neutral sentiment regarding the phrase “cancer survivor” (2 tables from the study are attached below).

Some limitations of the study were that survey respondents were primarily white women, and the overwhelming majority had been treated for breast cancer. Minorities, men, and those with other cancers were under-represented in this study. Despite these limitations, the authors concluded that “the term ‘cancer survivor’ does not serve well many of the people it is meant to describe.”   

Full Article: Is it time to reconsider the term “cancer survivor”?

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”

19 December 2018

A study recently published in the Annals of Internal Medicine noted that breast cancer risk increases after childbirth, peaking at about 5 years after delivery. The increased risk was seen to persist for over 20 years.

The Annals study pooled the results from 15 prospective series. They found that in women with prior pregnancy, who had their most recent child 3 – 6.9 years before the study period, there were 41 excess breast cancer cases per 100,000 women at age 45, 170 excess cases per 100,000 at age 47.5, and 247 per 100,000 women at age 50. These numbers, while statistically significant, are relatively low. However, they may of course be considered important to an individual woman, deciding whether or not to have children. 

The authors discussed that proliferation of breast cells during pregnancy and the post-partum microenvironment may play roles in facilitating and promoting abnormal cellular proliferation and mutation. There was a protective (not preventative) effect of breast feeding. In addition, as this study conflicts with prior research noting a protective effect of pregnancy in terms of breast cancer development, the authors suggest that this protective effect may relate more to breast cancer that develops at the “peak ages” (after 60) rather than in younger women.

As this study was a pooled analysis of other studies, information on breast feeding was not available for all patients, there were some patients where it was not possible to distinguish if breast cancer developed during pregnancy or during the immediate postpartum period, and there was limited data on breast cancer subtypes.

The impact of pregnancy on recurrence risk in patients who have been treated for breast cancer is an area of active research. A 2013 study demonstrated that patients who became pregnant after being treated for an estrogen-receptor positive breast cancer did not have increased risks of cancer recurrence. In addition, there is an ongoing cooperative group clinical trial, the POSITIVE study, evaluating outcomes of women who have been treated for breast cancer and then interrupt endocrine therapy treatment for pregnancy.

My take-home points from the Annals study are that there seems to be an association (which is very different from cause and effect) between pregnancy and development of breast cancer at a young age, but the absolute number of increased breast cancer cases are relatively small. I do not think this study should discourage women from starting a family if they want to have children, and the authors have not recommended enhanced breast cancer screening for women who have been pregnant. All women are at risk for breast cancer, and pregnancy may increase short term risk. Of course, any new breast finding or change should be evaluated, whether a woman has had children or not. 

Additional Information:
HealthLine -Women Have Higher Risk of Breast Cancer After Childbirth
NY Times-Breast Cancer Risk May Rise After Childbirth, but is Still Low

10 December 2018

Being overweight after menopause is associated with an increased risk of breast cancer. But a new study suggests that our traditional measure of overweight, the body mass index (BMI) may not tell the whole story.

A recent study, published in JAMA Oncology, performed detailed body composition analysis on 3000 women who were of normal BMI. They found that among these women, those with increased levels of body fat (especially in the truncal area – “belly fat”) had higher risks of estrogen receptor positive (ER+) breast cancer compared to women with lower body fat levels. In addition, the women with higher body fat levels also had higher levels of inflammatory markers as well as other metabolic abnormalities. 

This suggests that maintaining a healthy weight may not be enough. Muscle mass declines with age, so even if weight is stable, there is a slow but steady increase in body fat. Regular exercise can certainly help to maintain muscle mass and it also helps decrease the level of inflammatory markers. 

The authors note that more study is needed to better understand the links between body fat and breast cancer, but it is very clear that there is no way around it – exercise is essential for good health.

Additional Information:
NBC News: Belly fat increases risk of breast cancer despite normal BMI
CNN – Body fat levels linked to breast cancer risk in post-menopausal women

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

 

10 May 2018

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

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

Genetics:

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

Breast Imaging:

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

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

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

 Systemic Therapy:

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

Immunotherapy / Liquid Biopsy:

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

 

Diet and Hormone Replacement Therapy:

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

 

Changing Paradigms – Avoiding Surgery for DCIS and Neoadjuvant Patients

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

Lifetime Achievement Award

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

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

1 February 2018

February is heart health month!

It is well known that some breast cancer treatments including certain chemotherapy agents, trastuzumab (brand name herceptin – used for Her2/neu over-expressed cancers), and radiation therapy have the potential to cause damage to the heart. Echocardiograms and other monitoring tests are often performed during and after treatment for patients receiving certain chemotherapy medications and trastuzumab. We also try to tailor our treatment as much as possible to the individual patient’s tumor when treatment recommendations are made. Genomic tests such as the Oncotype Dx or MammaPrint help identify “low risk” patients that do not need chemotherapy.

In addition to regular monitoring, it is important that women who have been treated for breast cancer focus on the lifestyle factors that can improve heart health, such as regular exercise and a healthy diet. Women over 65 who have been treated for breast cancer are more likely to die of heart disease than the breast cancer, and all of the factors that improve heart health also decrease the risk of breast cancer recurrence.

Washington Post – Breast Cancer Treatments Can Raise Risk of Heart Disease
Forbes Online – Reasons Not to Freak Out About Risk of Heart Disease After Breast Cancer

19 December 2017

Up to 70% of patients treated for breast cancer experience some degree of cognitive dysfunction (more commonly known as “chemobrain”) during and immediately after treatment, and the symptoms may persist in up to 15-25% of patients. The impact on quality of life and ability to work varies; patients may experience forgetfulness, challenges with multitasking, and difficulty finding words and may even struggle to learn new information. Older patients are more likely to be affected but any patient who has been treated with chemotherapy or even endocrine therapy may note changes in mental function. Multiple factors contribute to the development of cognitive dysfunction, including toxicity of the chemotherapy agents specific to the brain and nervous system as well as other medical conditions, genetic factors and aging. The diagram below is from a recent review in the Journal of Oncology Practice (Lange, Joly) and demonstrates the complex interactions:

Persistent cognitive impairment after treatment can have significant negative effects including reduced adherence to oral medications, diminished self-confidence, and negative impacts on personal and work relationships. It can be challenging, especially in older patients, to sort out which symptoms are related to treatment versus aging and possible neurologic disease.

Unfortunately, while there has been an awareness about treatment related cognitive impairment for some time (especially among patients!) this is a relatively new area for research. An editorial accompanying the Journal of Oncology Practice article (Vardy, Dhillon) notes that as the specific mechanisms by which cognitive dysfunction develop are not known, there are few evidence-based recommendations for prevention or treatment. In addition, studies often show little correlation between a patient’s subjective assessment of their cognitive function and performance on a standardized test designed to be more objective. Factors such as anxiety, depression, and fatigue are associated with (patient) perceived cognitive impairment, but are only weakly associated with objective measures of impairment.

Complicating matters further, the authors note that cognitive rehabilitation programs have been shown to improve subjective cognitive function, but the results are mixed regarding improvement in objective measures.

A second editorial (Baer) provided some practical guidance. The author recommended that physicians work with their patients to review and streamline medication lists, eliminating medications for anxiety, pain and sleep if no longer needed. Basic lifestyle patterns such as sleep habits and diet and exercise routines should be discussed. Patients should be encouraged to start a daily exercise program (with physical therapy referral if needed). Laboratory studies to assess for anemia, vitamin deficiencies and thyroid function should also be performed with corrective action taken if indicated. Coordination with the patient’s primary care physician should take place to ensure that other medical problems such as diabetes, hypertension, and sleep apnea are controlled as much as possible. If depression and/or significant anxiety are present, these need to be addressed and treated. Yoga and other meditative practices have also been suggested.

Additional research is certainly needed. In the meantime, patients should should realize first that the changes they are experiencing are real. Patients should be encouraged to discuss their symptoms and possible solutions with their treatment team.

The articles referenced above are behind a “paywall”. If anyone is interested in the full text article please feel free to email me: contact at drattai dot com and I will be happy to provide them.