24 June 2018

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

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

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

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

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

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

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

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

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

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

 

4 June 2018

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

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

Sample Oncotype Dx Report

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

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

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

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

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

Additional information from the ASCO Post 

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

15 April 2018

Press coverage of a study recently published in the journal Science Translational Medicine has raised a lot of eyebrows and may be causing unnecessary worry in patients. The headline in USA Today noted “Healing process after breast cancer surgery may trigger cancer to spread, study says.”

Not mentioned in the headline: the study was performed in mice. Mice were injected with breast cancer cells, developed tumors, and then underwent a surgical procedure to implant a small sponge, I presume similar to the surgical gauze that is used in the operating room. Note – the mice did not have traditional breast cancer surgery. The study found that the mice that underwent the surgical procedure had a higher rate of developing metastatic breast cancer – spread to other organs of the body. They also found that when mice received anti-inflammatory agents (meloxicam – brand name Mobic – was used in the study), they had a lower rate of developing metastatic disease.

It is well known that surgery can cause an inflammatory response and alteration in immune system function.. It is not entirely clear what that means for the average patient undergoing breast cancer surgery, and we certainly do not see metastatic disease develop in the majority of patients treated with surgery. If inadvertently left behind in a surgical wound (a very rare event), surgical gauze causes significant swelling, pain, inflammation and often infection – not at all similar to the healing process from lumpectomy or mastectomy. We cannot make assumptions from this mouse study if the use of anti-inflammatory agents after surgery would be helpful in human patients.

The take-home point for me is from my quote in the Stat News coverage: “I do not know if this mimics the potential effect of a lumpectomy or mastectomy, but the inflammatory response to an implanted foreign body would be expected to be quite robust,” said UCLA’s Dr. Deanna Attai, a past president of the American Society of Breast Surgeons. That inflammation, not surgery, might be awakening dormant cancer cells. Nevertheless, she said, “this study and the handful of others like it certainly are interesting and warrant further study.”

Until we have more information, and studies in humans with breast cancer, breast cancer surgery remains an important component of treatment.

Health News Review coverage: A breast cancer study in mice gets big headlines, setting up potential for patient “disaster”, experts say

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

31 January 2018

In women who undergo lumpectomy for breast cancer, the likelihood of another cancer developing in the treated breast can range from 0.2 – 1.0% per year, and this rate can be decreased with the addition of endocrine therapy such as tamoxifen or an aromatase inhibitor. The likelihood of developing a contralateral (opposite side) breast cancer is about 0.6% per year, and can also be reduced by endocrine therapy. Prior to making a decision on lumpectomy versus mastectomy, women commonly ask about the possible need for additional biopsies and procedures.

A study published in JAMA Surgery reviewed 2 large insurance databases to determine the frequency of breast biopsy after breast cancer treatment. Over 120,000 cases were analyzed. The researchers found that 15-23% of patients underwent subsequent biopsies during the 10 year period evaluated. 20-30% of these patients underwent additional cancer treatment.  Factors associated with lower biopsy rates included the use of endocrine therapy and older age. The use of partial breast irradiation (brachytherapy) was associated with a higher biopsy rate.

As this was an insurance claims database review (review of billing codes, not actual patient charts or medical records), it is not possible to know if biopsies were performed on the side of initial cancer or the opposite side, except in patients initially treated by mastectomy. In addition, a limitation of all claims database studies is that if the billing and diagnosis codes are not correctly entered, the information obtained will not be accurate. However, given the large number of claims reviewed, this study at least provides an estimate for patients to use when weighing the options of lumpectomy or mastectomy.

1 January 2018

The American Joint Committee on Cancer (AJCC) has recently updated the staging system used for breast cancer. Cancer stage refers to the amount of cancer (size of the main tumor, spread to lymph nodes or other areas). The definitions of each stage vary depending on cancer type. Cancer stage often correlates with outcomes, and treatment recommendations usually take into account stage of disease.

As our knowledge of tumor biology increases, it has become clear that stage is not the only factor that impacts prognosis. Tumor biology and behavior are very important, and in some cases may be more important than stage. A small tumor with aggressive behavior characteristics may may result in worse outcomes compared to a larger, but slower growing cancer. The 8th version of the AJCC staging system for breast cancer now takes into account tumor biology. Factors such as cell grade, ER/PR and Her2/neu status, and even the results of tumor genomic tests will be incorporated into the clinical and pathological prognostic stage. Taking into account these biologic factors means that the stage will have more meaningful prognostic information. Some larger tumors will now be considered stage I, and some smaller lesions will be upstaged based on their biology. In a large validation study performed by researchers at the University of Texas MD Anderson Cancer Center, 31% of patients were upstaged, and 20% of patients were downstaged. The updated prognostic stage performed better (in terms of predicting patient outcomes) than the standard anatomic stage.

The new staging system will take some getting used to. The tables used to help determine clinical and pathologic prognostic stage are 5-6 pages long. However, this new system will give us more meaningful information in terms of prognosis and outcomes. Just please be patient with your physician when you ask “what is my stage?” – it is no longer a simple question!

Additional Information:
American Cancer Society CA Cancer Journal: Breast Cancer – Major Changes in the AJCC 8th Edition

26 December 2017

A study recently published in the Journal of the American College of Surgeons evaluated patient perceptions regarding knowledge about their breast cancer surgery. An online survey was distributed via email to patients who had participated in previous online surveys and had agreed to be contacted again. Enrollment quotas were set for geographic area, insurance status, and income level to try to achieve a varied sample population. In the analyzed sample, 215 patients underwent lumpectomy, 140 underwent mastectomy, and 132 reported that they had undergone both procedures.

The study showed that only 47% of patients who underwent a lumpectomy and 67% who underwent a mastectomy felt fully informed about their treatment choice. About 30% of patients who underwent lumpectomy or mastectomy and about 20% of those who underwent both procedures felt that making a quick treatment decision was more important than thoroughly researching all of the options. The majority of patients reported that they “somewhat” or “strongly” felt that more time would be helpful to make their decision.

60% of patients who underwent lumpectomy obtained a 2nd surgical opinion. 45% of mastectomy and 87% of patients who underwent both procedures obtained a 2nd surgical opinion. Over 50% of women reported receiving additional information from other physicians, websites, and family / friends. A little over 30% of patients sought out information from online blogs and discussion groups.

The study has several limitations, the most important being that a variable amount of time might have elapsed from the time of the patient’s surgery to the time of the survey, and responses may have been influenced by “recall bias”. In addition, the patient population was primarily Caucasian and college-educated. However, this study along with other research clearly shows that we have a long way to go in terms of better informing our patients about their surgical options for breast cancer treatment. This study also shows that patients still feel a sense of urgency to make quick decisions about their treatment.

Physicians are under increasing pressure to see more patients, which limits the amount of time available for each consultation. However, physicians have a responsibility to ensure that patients receive a balanced discussion of their options and need to make themselves available to answer questions. Patients should not feel pressured to make quick decisions, and 2nd opinions can be helpful prior to making a final decision. The authors conclude that “Patients who are completely informed of all their treatment options will make higher-quality shared decisions about treatment and will experience better long-term survivorship outcomes” and I couldn’t agree more.

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.

9 November 2017

In patients with a common form of breast cancer, known as estrogen receptor (ER) “positive”, endocrine therapy is often recommended after other treatments such as surgery, chemotherapy, and radiation are complete. Tamoxifen, most commonly used in pre-menopausal women, blocks the estrogen receptor on the breast cell, so estrogen cannot impact cell growth. In post-menopausal women, aromatase inhibitors (AI) are commonly used – these medications block the production of estrogen in the fat cells – a primary source of estrogen after menopause. Historically, these medications have been used for 5 years after completion of other treatment, although there are some studies suggesting longer courses may benefit certain patients. However, longer courses of therapy are associated with a higher incidence of side effects.

A study just published in the New England Journal of Medicine demonstrated that after 5 years of endocrine therapy, patients have an increasing risk of breast cancer recurrence with long term follow up. The authors evaluated individual patient data from a large database of randomized trials. They found that in patients with stage I tumors (tumor less than 2 centimeters and no lymph node involvement) the 20 year risk of recurrence was approximately 13%. In patients with 4-9 involved nodes, the risk ranged from 34-41% depending on the size of the main tumor.

This study is important as it confirms what many of us see in our practices – that breast cancer can and does recur, even many years after therapy. However, it also raises an important discussion point about our treatments. Studies have estimated that as many as 30% of women prescribed endocrine therapy stop treatment due to side effects which significantly interfere with quality of life such as menopausal symptoms, bone and joint pains, bone loss (osteoporosis) and fracture, and mental status changes (“chemobrain”). Patients should discuss any of these symptoms, especially if they are considering stopping their medication, with their physicians. Lifestyle changes, exercise programs, and medications may be of benefit. It is also important to understand that despite all appropriate treatment, cancer can and does come back – so health maintenance and surveillance are important even long after cancer therapy has ended.