8 May 2017

As a past-president of the American Society of Breast Surgeons I am probably more than a little biased. However, as always, the annual meeting held April 26-30th in Las Vegas was terrific. Topics including the full spectrum of breast disease, including benign and high risk lesions, genetic testing, breast cancer diagnosis and treatment including medical and radiation oncology updates, and metastatic disease.

The press briefing highlighted 3 abstracts which showed that:

  • Modern therapy for inflammatory breast cancer is associated with better outcomes than historically seen
  • Post-treatment lymphedema is related to a combination of treatments including surgery, radiation therapy, and chemotherapy – not just from surgery
  • Patients with DCIS have a 5 year risk of developing a cancer in the other breast of 2.8% and a 10 year risk of 5.6%, and patients should be discouraged from undergoing bilateral mastectomy for this condition. Developing a new cancer in the previously treated breast was twice as likely as developing a new cancer in the opposite breast, and the use of tamoxifen reduced the likelihood of any recurrence.

Dr. Nathalie Johnson moderated a pre-meeting course on Building a Breast Cancer Survivorship Program. I was invited to speak on Traditional Versus Virtual – Options for Patient Support and Education. Just as it can be challenging to choose between cake and ice cream (2 really good things), patients note advantages to both in person and online support and education. It doesn’t have to be one or the other – do what works for YOU! My slides are posted on SlideShare.

During the general sessions, a few topics stood out to me:

Dr. Shelley Hwang from Duke University spoke on DCIS subtyping and overtreatment. She noted that DCIS now comprises over 20% of all mammographically detected breast cancer. It is considered a “non-obligate precursor” of invasive cancer – the rate and likelihood of progression to invasive cancer are not clearly known. However, it is clear that some patients will never exhibit progression to invasive disease, and she discussed this in the context of thyroid and prostate cancer – two situations where we know that treatment in some patients will not provide the patient any benefit. The challenge is to sort out which patients will benefit from treatment and which ones will not. The COMET study is currently enrolling patients with low grade DCIS to in an attempt to help answer these questions.

Dr. Virginia Herrmann from Washington University in St. Louis spoke on non-genetic breast cancer risk factors. This is an important topic and I believe one that doesn’t get covered enough. She noted that hormone replacement therapy does increase risk – although the incremental risk is small and is seen only after about 5 years of use. However, longer term use does result in higher risk. Increased body mass index (BMI) is associated with risk – the risk of breast cancer is 30% higher in patients with a BMI greater than 31 kg/m2 compared to a BMI of 20 kg/m2. She noted that there is a linear relationship between alcohol intake and cancer risk, noting a 10% increase in risk for each 10 gm/day (for wine this is a little over 3 oz) increment in alcohol consumption. The risk is most associated with post-menopausal breast cancer, although in the study she quoted, only alcohol intake during age 50s was associated with an increased risk of postmenopausal breast cancer. She noted the association of ionizing radiation and breast cancer, and young women who received mantle (chest area) radiation for Hodgkin’s lymphoma have a markedly increased risk for developing breast cancer. She noted that breast cancer risk is increased in smokers, correlated with smoking intensity and duration. Finally, she noted the increased risk of breast cancer among soldiers stationed at Camp LeJune related to contaminated drinking water (tetrachloroethylene and trichloroethylene).

Dr. Tiffany Traina, a Memorial Sloan Kettering medical oncologist, gave a brief presentation about triple negative breast cancer: Searching For the Magic Bullet. There are several promising treatment strategies including targeting androgen receptors, the use of PARP-inhibitors in patients who have BRCA gene mutations, antibody-drug conjugates, immune modulating approaches, and targeted therapies based on tumor genomic profiles. Stay tuned – much more to come over the next few years related to this aggressive breast cancer subtype.

Dr. Lisa Newman, from the Henry Ford Health System in Detroit, spoke on Breast Cancer Outcomes: Disparities versus Biology. I have heard her speak on this topic multiple times over the years and always enjoy her excellent presentations. She noted that the incidence of breast cancer in black women is increasing, now close to that in white women. However, mortality rates for black women are higher than those for white women. There is an increased frequency of triple negative breast cancer in black women. She is involved in a research initiative evaluating the association between African ancestry and high risk breast cancer in white American women, African American women, and women in Ghana, including studying novel aspects of tumor biology and breast cancer stem cells – she is asking the question “are there differences in the oncogenic potential of mammary tissue that are associated with ancestry”? She concluded with what I felt was a powerful slide – 60% – 43% – 20%. Those were the survival rates for passengers on the Titanic who were in 1st – 2nd – 3rd class. She noted that healthcare outcomes are often dependent on access to care, and ended with a quote from Dr. Martin Luther King, Jr.: “Of all the forms of injustice, inequality in health care is the most shocking and inhumane”.

Dr. Stephen Edge, from the Roswell Park Cancer Institute, gave an update on the new American Joint Commission on Cancer staging system (AJCC 8th edition). Currently we stage breast cancer based on tumor size and lymph node status. However, it is recognized that that tumor biology plays an important role in prognosis and in some patients it may be more important that tumor size. The new staging system will incorporate tumor grade, Her2/neu status, ER/PR status, and Oncotype Dx status (if available) and should more accurately reflect prognosis. There are 422 lines in the new staging system – it will be impossible to memorize! Thankfully, he noted that the AJCC is working on a staging app.

The last day of the meeting held some great sessions, and the meeting room remained packed up until the very last minute. Dr. Ann Partridge from Dana Farber discussed special considerations in the young breast cancer patient. She noted that the disease is different, the patients are different, and the treatments should be different. Younger women have a higher likelihood to have more aggressive subtypes such as Her2/neu over-expressed and triple negative, and have lower survival rates than older women – even in those with the ER positive breast cancer. However, she cautioned not to over-treat patients based only on age. She noted that young age is not a contraindication for breast conservation, and that there is no clear improvement in mortality in patients who undergo more extensive surgery. She noted the need for improvements in treatment and support, including focused research and guidelines, which should lead to better outcomes.

Dr. Irene Wapnir from Stanford spoke on fertility preservation issues. She noted the various fertility options including medications and procedures. She also reviewed the POSITIVE trial, which will be assessing the risk of breast cancer relapse in patients who temporarily stop endocrine therapy to permit pregnancy, as well as to evaluate factors associated with successful pregnancy after interruption of endocrine therapy. She also stressed that fertility preservation should be discussed with any woman of childbearing age, whether or not she has had a prior pregnancy or a child – physicians won’t know what is important to their patients unless we ask!

Dr. Katherina Zabicki Calvillo from Dana Farber discussed breast cancer in pregnancy. She noted that 0.2-4.0% of breast cancers are diagnosed in pregnant patients – about 1 in 3000 pregnancies. She also noted that given the overall delay in childbearing (and the association of increasing age with breast cancer), the incidence of pregnancy-associated breast cancer will increase. Delays in diagnosis are related to hormonal changes which affect breast tissue making the exam more challenging, and that many patients and physicians assume that masses are related to pregnancy. She stressed that pregnancy termination is usually NOT required, but a multidisciplinary team approach is required. Many of these patients present in more advanced stages, but stage-for-stage, the prognosis is similar to non-pregnant patients with breast cancer. Chemotherapy can be given after the first trimester, but hormonal and Her2/neu targeted therapy should be avoided. She noted that mastectomy should be performed in the first and early 2nd trimester, and discussed the challenges of immediate reconstruction. Breast conservation could be considered in the late 2nd or 3rd trimester with post-lumpectomy radiation planned for after delivery.

Dr. Kevin Hughes from the Massachusetts General Hospital reviewed research studies that have found that in women over the age of 70 with early stage breast cancer, radiation therapy after lumpectomy may not be necessary.  The CALGB 9343 study showed that survival rates were the same whether women received radiation therapy or not. Radiation therapy did reduce the likelihood of cancer returning in the breast (local recurrence) from about 4% in the untreated patients to about 1% in the treated patients (after 5 years of follow up). However it is important to realize that the majority of women in that study were treated with endocrine therapy, which can help reduce the risk of local recurrence. As with many decisions regarding breast cancer treatment, a careful discussion of the risks and benefits of each option is necessary.

Dr. Tina Hieken from the Mayo Clinic gave a very interesting talk on the microbiome and the impact on breast cancer. We normally co-exist with many bacteria – we have ten times the more microbial cells compared to human cells. These microbes carry out metabolic reactions that can be essential to human health. The genetic material (genome) of our microorganisms is called the microbiome. She and her colleagues studied breast tissue from women with and without breast cancer and found that the background breast microbiome is different in women with breast cancer compared to those with benign conditions. She concluded by noting that the future may involve using a microbial pattern to predict breast cancer risk, exploiting the microbiome to enhance treatment response, and that there may also be implications for a cancer prevention vaccine. The Washington Post recently covered her research – definitely worth a read for more information.

Dr. Anthony Lucci from MD Anderson discussed the “Ongoing Saga of Circulating Tumor Cells”. We would all like to see the day when a blood test can tell us with certainty if cancer has developed or returned – but we’re not there yet. After reviewing several studies evaluating both circulating tumor cells (CTC) and circulating “cell free” DNA, he concluded that this information does provide prognostic information in both metastatic and non-metastatic patients, but is not in the current ASCO or NCCN guidelines for guiding treatment. Combining the CTC status with response to preoperative chemotherapy may identify a low risk subset of patients, but noted that additional studies are needed before we can reach the ultimate goal which is improving outcomes by monitoring and responding to CTC and cell free DNA levels.

Dr. Manjeet Chadha from Mount Sinai spoke on repeat lumpectomy after prior lumpectomy and breast radiation. Traditionally, mastectomy has been recommended if cancer returns after lumpectomy and radiation therapy. On average, there is about a 10% risk of “in breast” recurrence after lumpectomy and radiation, but this will vary based on tumor and treatment type. She reviewed several studies evaluating the different types of focused or partial breast radiation that may be used in selected patients who experience recurrence of their breast cancer. She also called for additional studies in this area.

One of the last talks was by Dr. Mehra Golshan from Dana Farber. He spoke about the decision whether or not to operate on patients with breast cancer who present with Stage IV (metastatic) disease. Traditionally, we have not recommended surgery for patients with metastatic breast cancer as these patients were not expected to have long survival, and it was not felt that removal of the main tumor would impact survival. Evaluating existing studies has also been challenging because while some have shown a benefit to removal of the main tumor, the patients who underwent surgery in those studies tended to be younger and healthier. He concluded by noting that surgery in patients with Stage IV breast cancer is not standard of care, but some studies do support this practice. It is recommended that these patients be evaluated in a multidisciplinary forum and that treatment choices be individualized.

 I returned from the meeting exhausted but energized. In addition to the scientific content, the meeting is an opportunity to connect with friends and colleagues across the country. I’m already looking forward to ASBrS 2018!

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

20 March 2017

Over 50,000 women in the US are diagnosed every year with ductal carcinoma in-situ (DCIS), also known as Stage 0 breast cancer. DCIS is most often diagnosed on screening mammography and usually presents as a cluster of calcium deposits rather than a lump. In cases of DCIS, malignant appearing cells grow within the milk duct, but do not invade through the wall of the milk duct. DCIS is considered to be a “non-obligate precursor” to invasive breast cancer – it has the potential to develop into invasive disease, but this does not happen in all cases. However, we traditionally have treated DCIS and invasive cancer in a similar fashion – with surgery, radiation therapy and endocrine therapy. It has become clear over the past several years that low grade DCIS is likely a different disease compared to high grade DCIS. Aggressive treatment of low grade DCIS may not improve outcomes but has the potential to cause significant harms.

A new clinical trial has opened for patients with low risk DCIS. The COMET Trial (Comparison of Operative to Monitoring and Endocrine Therapy) is currently enrolling patients under the direction of Dr. Shelley Hwang, a breast surgical oncologist at Duke University. Eligible patients will be randomized to guideline concordant care (standard therapy) versus active surveillance. The primary objective is to evaluate the rate of invasive breast cancer development in the active surveillance group. Secondary objectives include assessments of quality of life and anxiety. In addition, clinical outcomes including mastectomy and breast conservation rates, overall survival and breast cancer specific survival, and ipsilateral (same side) invasive breast cancer rates will be assessed.

The COMET study is not the first to evaluate non-operative therapy for DCIS. The LORIS and LORD trials are already enrolling patients in Europe. A UK-funded initiative known as PRECISION (Prevent Ductal Carcinoma In Situ Invasive Overtreatment Now), headed by the Netherlands Cancer Institute, will collaborate with all three trials.

It is always challenging to go against standard treatment, especially when that means less treatment. It took almost 50 years after the death of Sir William Halsted (“Halsted Radical” mastectomy) for surgeons to accept less invasive surgical procedures. Many patients (and physicians) may feel uncomfortable not removing cells that have been labeled “cancer”. It is important to recognize that lack of surgery does not mean no care – “active surveillance” is now an accepted management strategy for some cases of low grade prostate cancer. Our treatments come with real long term side effects and toxicity. The COMET study is a step in the right direction to help determine which patients may safely avoid aggressive treatment.

Additional Information:
DCISOptions.org
DCIS, Continued…
Slideshare – Are We Overtreating DCIS?
CBS News: Dr. Laura Esserman – When is it OK Not to Treat Cancer?
HealthNews Review Podcast: Dr. Laura Esserman – The DCIS Dilemma
HealthNews Review Podcast: Active Surveillance for Prostate Cancer

26 December 2016

Approximately 75% of breast cancers express the estrogen receptor – we term these breast cancers ER positive (ER+) or hormone-sensitive. Endocrine therapy refers to using medications to exploit this cancer cell property. Tamoxifen is used in premenopausal women and it blocks the estrogen receptor. In post-menopausal women, aromatase inhibitors (AI) are used which prevent estrogen from being produced (primarily in the fat cells after menopause).

In June, a study was presented which suggested that 10 years of endocrine therapy in post-menopausal women might be superior to 5 years of treatment, which had been the standard. The study noted that disease free survival was improved and development of new breast cancers were reduced in the extended therapy patients, but there were more side effects. A conclusion was that extended therapy might be appropriate for higher risk patients – those who based on certain tumor factors we suspect might have a higher risk of recurrence. A challenge has been that we do not have good tests to tell us with certainty which patients will truly benefit from a longer course of therapy.

At the 2016 San Antonio Breast Cancer Symposium, 3 studies were presented which addressed the issue of extended endocrine therapy in post-menopausal women. In all 3 studies, extended endocrine therapy with an AI did not improve disease free survival, in contrast to the study presented in June.  A lack of survival benefit does not mean that extended therapy is not worthwhile, as noted in this ASCO Post article, and one of the studies did show improvements in distant metastases and contralateral (other side) breast cancers. Dr. Michael Gnant, who discussed the studies at the meeting, noted that “The trials did not reach the necessary statistical levels to demonstrate a clear benefit for aromatase inhibition extension. Extending aromatase inhibitor therapy may be a good idea for many patients after 2 to 5 years of tamoxifen, but after initial treatment with an aromatase inhibitor, the benefits and risks must be carefully balanced on an individual basis. We are going to need the ‘art of medicine’ here.”

While ER+ breast cancers tend to be “better behaved”, we know that these patients are at risk for relapse many years after initial treatment. This knowledge has to be balanced with the real side effects women experience from taking the medications. Common side effects of the AIs include joint and bone pains, vaginal dryness, hot flashes, and bone loss. Deciding whether or not to continue on the medications in the setting of significant side effects is also difficult for patients, who then have concerns about “not doing enough” to reduce the risk of cancer recurrence. More research is needed to develop both tests to help predict which patients will actually benefit from extended therapy, and treatments with fewer side effects,

 

25 August 2016

A study published today in the New England Journal of Medicine reports on the 5 year results of the MINDACT (Microarray In Node-negative and 1 to 3 positive lymph node Disease may Avoid ChemoTherapy) trial. This study was designed to evaluate the use of a tumor gene signature test (MammaPrint) compared with standard factors to assess the need for chemotherapy.

This study enrolled 6693 women in 112 countries who had undergone surgery for Stage I and II breast cancer. Once patients were registered, they were stratified based on risk. Risk was assessed both by the MammaPrint (MP) score as well as standard clinical – pathological markers (CP) such as tumor size, grade, ER/PR status, and Her2/neu expression calculated using the Adjuvant! Online tool.

2745 patients who had low risk MP and CP scores did not receive chemotherapy; 5 year metastasis-free survival in this group was approximately 97.6%. These findings were consistent with those reported using a different genomic test, the Oncotype Dx test, which also demonstrated good results without chemotherapy in low risk patients. 1806 patients who were high risk by both assessments received chemotherapy and 5 year metastasis-free survival in this group was approximately 90.6%.

The other 2 groups were those with discordant results, and these patients were randomized to either chemotherapy / endocrine therapy or endocrine therapy. The results for the 592 patients with high risk MP scores but low risk CP assessment are pending. The recently published study focuses on the 1550 patients with low risk MP scores but were high risk based on CP assessment.

The study demonstrated that in these patients, chemotherapy provided a slight benefit: 1.5% improvement in survival without metastatic disease, 1.4% improvement in overall survival, and 2.8% improvement in disease free survival. The study was not powered or designed to determine if these differences were statistically significant.

On the surface, the study seems to indicate that chemotherapy is of little to no benefit for those patients with low risk MP scores and high risk CP features. There is no question that genomic tests such as the MammaPrint have revolutionized our treatment recommendations. We now have the ability to obtain more detailed information about an individual patient’s tumor biology, which can help us guide treatment decisions. It is clear that our traditional methods of assigning risk such as tumor size, grade, and node status, do not always tell the whole story, and it is no longer acceptable to recommend chemotherapy “just to be sure”. The use of genomic tests in appropriate patients is very important to avoid the real dangers of over treatment. But as this study was not designed to assess statistical significance (rather, “non inferiority“), can we say that the benefits demonstrated from chemotherapy may not be important for an individual patient?

Median follow up in this study was was 5 years. 48% of patients were lymph node positive, 93% had grade 2 or 3 disease, and 34% were age 50 or younger. These factors are more often associated with an earlier risk of recurrence, so 5 years may be sufficient to note a difference in survival rates. It was also stated by the authors that “adjuvant chemotherapy exerts most of its beneficial effects early in the course of the disease”. However, they also noted that many of the tumors were ER+, which may recur well past 5 years. 10 year follow up is planned.

In an accompanying editorial, Drs. Hudis and Dickler point out that “although we may all agree that a 1% risk of distant metastasis at 5 years on the basis of genomic testing eliminates any potential benefit of chemotherapy, at what point would we begin to have differing opinions and perhaps mixed results from clinical trials? Answering this question is even more challenging, given that all chemotherapy is not the same in terms of efficacy or toxicity and that patients and health care providers bring subjectivity and personal values to their treatment decisions.”

As was pointed out during a recent online exchange (by a woman who had a low recurrence score and now has metastatic disease), these tests are not guarantees. While the numbers are low, some women in the low risk group developed metastatic disease. It is not known if chemotherapy would have been of benefit, but it does demonstrate how percentages are applicable to populations, not necessarily to individuals. We do not yet have a test that will predict the outcome with 100% certainty. The test results should be presented as part of a discussion which includes the patient’s preferences, values and concerns – concerns regarding cancer recurrence as well as potential side effects of therapy.

09 June 2016

A study presented at the recent American Society of Clinical Oncology meeting evaluated the use of extended endocrine therapy in post-menopausal women. I’ve covered some of the basics of endocrine therapy for breast cancer in a previous post. In 2012, results of the ATLAS Trial were published, and found that when tamoxifen was given for 10 years instead of the standard 5, improvements were noted in overall and disease free survival.

Up until this point, no study has demonstrated similar findings for post-menopausal women taking aromatase inhibitors. Results of the MA.17R study were reported at the 2016 ASCO meeting, Patients in the study had already completed at least 5 years of endocrine therapy with the aromatase inhibitor letrozole. They were then randomized to receive either an additional 5 years of letrozole or a placebo. Median follow up was 6.3 years.

The key study findings were as follows:
  Disease free survival was 95% in the treatment group and 91% in the placebo group, a 34% reduction. This was statistically significant.
–  Contralateral breast cancer (a new cancer developing in the opposite breast) occurred in 1.4% of the treatment group, and 3.2% of the placebo group a 58% reduction. This was also statistically significant.
–  Overall survival was the same in both groups.
–  More bone fractures (14% vs. 9%) and new-onset osteoporosis (11% vs. 6%) were seen in the patients undergoing extended endocrine therapy – it is well known that these medications accelerate bone loss. These findings were statistically significant.
– Rate of discontinuing therapy was 5.4% in the letrozole group, and 3.7% in the placebo group.

Several points were brought up in the discussion immediately following the presentation as well as in post-plenary “town hall” style session held later in the day, including:

–  It is not clear what the long-term effects of medications used to treat bone loss will be – if patients are on endocrine therapy for longer periods of time, they likely will need to be on the bone protective medications for longer as well.
–  Reported quality of life was similar in both groups, as reported by Dr. Julie Lemieux. However, as Dr. Don Dizon noted: “without compromising quality of life” isn’t the same as “everything’s peachy.”

– It was noted that the patients enrolled in the study were self-selected which may bias the results. As they had already completed at least 5 years of letrozole therapy, these patients likely had few existing side effects from treatment. Concern was raised in the post-plenary discussion that we may see more of an impact on quality of life if a broader population of women is treated with extended endocrine therapy.
Dr. Lisa Carey noted that adherence to endocrine therapy remains a significant issue in part due to medication side effects. While the rate of discontinuation of therapy in this study was low, this does not reflect real-world experience.

The disease free survival improvement and contralateral breast cancer reduction were widely reported in the press as percentages (34% disease free survival benefit, 58% reduction in contralateral breast cancer). It is important to realize that the absolute benefits are very small – only a few percentage points. While the results achieved statistical significance, they may or may not be significant to an individual patient. It is important that patients understand the concept of absolute risk vs. relative risk.

Professor Ian Smith, who discussed the abstract during the plenary session, concluded by saying that the MA.17R findings do not justify extended endocrine therapy in all patients. Rather, patients with more aggressive features such as larger tumors, positive lymph nodes, and higher cell grade may benefit. He called for physicians to carefully discuss the study results with their patients, and allow them to participate in the decision for or against extended endocrine therapy.

This conclusion prompted the following Twitter exchange with an oncology colleague:

While it should go without saying that we need to discuss study results as well as advantages and disadvantages of treatment with our patients, this point is not emphasized enough during national presentations. The lead author, Dr. Goss, commented during the post-plenary discussion that he is not specifically recommending extended hormonal therapy. Rather, he acknowledged that this is a decision that needs to be made by an individual patient, in consultation with her physician, after carefully reviewing all of the information. The study received a significant amount of media attention, and the discussion at the conference session was very spirited. At the end of the day, it’s important that patients to realize that we don’t have a definitive answer for the individual.

It is also important not to forget the impact of lifestyle factors in terms of reducing risk of recurrence. Regular exercise, weight maintenance, healthy food choices, and moderation in alcohol intake all will help reduce the risk not only of breast cancer recurrence, but also of cardiovascular disease, which remains the number one killer of women in the United States.

Additional Reading:
ASCO Post Overview of MA.17R
Changing Adjuvant Breast Cancer
Dr. Elaine Schattner in Forbes

 

 

9 November 2015

The American Society of Breast Surgeons Foundation has just launched a patient information website – Breast360.org. The site was developed by breast surgeons, and patient advocates have had input and oversight during the entire process. Please take a look, and feel free to provide feedback if you have a suggestion for additional content.

 

15 October 2015

A recent study has noted that African American and Hispanic women are more likely to be diagnosed with aggressive forms of breast cancer. Drs. Lu Chen and Christopher Lee published their findings, Racial Disparities in Breast Cancer Diagnosis and Treatment by Hormone Receptor and Her2 Status, in a recent issue of the journal Cancer Epidemiology, Biomarkers and Prevention.

Using information from SEER Registries, they identified 120,000 women, age 20 and over, diagnosed with invasive breast cancer between 2010-2011, with documented information about tumor stage, hormone receptor, and Her2 status. They evaluated the associations between patient race / ethnicity and stage at diagnosis as well as receipt of guideline-appropriate care. Findings included:

  • African American and Hispanic women were 30-60% more likely to be diagnosed with stage II-IV breast cancer compared with non-Hispanic white women
  • African American women had 40-70% risks of being diagnosed with stage IV breast cancer depending on tumor subtype
  • American Indian and Alaska Native women had a 3.9 times higher risk of stage IV triple-negative breast cancer
  • African American and Hispanic women were 30-40% more likely to receive non-guideline concordant care for their breast cancer

The findings reflect those reported earlier this year in the Journal of the National Cancer Institute. It is not news that African American and Hispanic women have worse breast cancer outcomes compared to other populations. They are more likely to be diagnosed at advanced stages, are less likely to receive guideline-appropriate treatment, and have worse overall survival. It is becoming clear that breast cancer is a different disease in women of different racial and ethnic backgrounds – they are more likely to have higher-risk subtypes. This study confirms these points, with the exception of survival, which was not assessed due to the short time period of data analysis (2010-2011). This emphasizes the need for continued research regarding the racial and ethnic variations in tumor subtypes.

Presentation at more advanced stage and lack of guideline-concordant care for African American and Hispanic women should be of concern to us all. This points to racial, ethnic and socioeconomic disparities in education, access to screening, and access to quality care. The authors concluded by stating:  “As contributors to racial / ethnic disparities in breast cancer are complex and multifactorial, continued efforts, especially targeted, culturally appropriate interventions, to address these disparities across different subtypes of breast cancer have the potential to reduce these long-standing disparities and hopefully close the existing survival gaps.”

29 September 2015

One of the most common questions asked by a newly diagnosed cancer patient is “Will I need chemotherapy?”. Almost everyone is aware of the toxicity related to chemotherapy, and the fact that it is a common component of cancer treatment. A recent study sheds some light on which patients can safely avoid chemotherapy.

We have known for many years that not all patients who receive chemotherapy will benefit from it – in some cases, less than 3% of patients benefit. We traditionally used measures such as tumor stage, tumor grade, and receptor status such as ER/ PR and Her2/neu. Since 2004, many of us have relied on the OncotypeDx test. This assay, which is performed on the tumor, analyzes 21 genes (of the cancer – different from genetic testing of the patient) that have to do with cell growth and proliferation. The score, which is reported as low, intermediate, or high, is used to help determine whether or not a patient will benefit from chemotherapy.

The initial studies leading to widespread use of the OncotypeDx test were retrospective. Many of the large national breast cancer trials had tissue saved from the original procedures. The OncotypeDx test was run on these tissue samples, and then was analyzed with respect to patient outcomes. Based on these studies, patients with low risk scores were advised not to undergo chemotherapy; chemotherapy targets rapidly dividing cells, and low-risk tumors simply will not respond. Conversely, patients with high risk scores were advised to undergo chemotherapy treatment. Based on these studies, we discovered that our traditional methods of determining who should receive chemotherapy were not very accurate.

A new study published in the New England Journal of Medicine is the report of the first prospective trial involving OncotypeDx testing. Dr. Joseph Sparano and colleagues reported on the Prospective Validation of a 21-Gene Expression Assay in Breast Cancer. In this study, patients with hormone-receptor positive, Her2/neu negative breast cancers, 1.5 – 5.0 cm in size, had OncotypeDx testing on their tumors. Patients with low-risk tumors received endocrine therapy (tamoxifen or aromatase inhibitors). Patients with high-risk tumors received chemotherapy. Patients with intermediate-risk tumors were randomized to either hormonal therapy or chemotherapy, as prior studies did not demonstrate a clear benefit from either class of treatment.

The current study reports on the low-risk group, which included 1626 women. At 5 years, fewer than 2% of patients experienced a local-regional (breast or lymph nodes) or distant / metastatic (spread to other areas of the body) recurrence.

The authors concluded that endocrine therapy is perfectly appropriate for patients with low-risk tumors, and chemotherapy would not add any significant benefit in terms of recurrence or overall survival. A criticism of the study was that follow up was only 5 years, but the authors note that the primary benefit of chemotherapy is in reducing recurrences within the first 5 years of treatment. Endocrine therapy is recommended for longer-term reduction in recurrence in these patients.

Dr. Clifford Hudis, of the Memorial Sloan Kettering Cancer Center in New York, wrote an accompanying editorial: Biology Before Anatomy in Early Breast Cancer – Precisely the Point. He noted that “this assay is the most rigorously tested option and provides proof of the principle that we can develop reproducible predictive results to select patients who should not receive chemotherapy. In that regard, it is one more step towards precision. There are more steps ahead.”

9 June 2015

Surgery doesn’t help women with early-stage breast cancer – that’s certainly a headline that will get attention. The recent NPR article referred to a study published in JAMA Surgery: Survival Benefit of Breast Surgery for Low Risk Ductal Carcinoma In Situ – A Population-Based Cohort Study(1). The study raises some very interesting points, but the NPR headline is misleading. Early stage breast cancer can refer to Stages 0, I, and 2, and the study cited only refers to low grade ductal carcinoma in situ.

In this study, researchers used the SEER database to identify fifty seven thousand cases of DCIS treated in the United States from 1988-2011. 2% of that group did not undergo surgery. The researchers evaluated breast cancer specific survival in the patients treated with and without surgery in relation to tumor grade. They concluded that there was no survival advantage to undergoing surgery in cases of low grade DCIS. For patients with intermediate grade DCIS, 10 year breast cancer specific survival rates were 98.6% in the group who underwent surgery vs 94.6% in the non-surgical group. For patients with high-grade DCIS, 10 year breast cancer specific survival was 98.4% in the surgical patients vs. 90.5% in the non-surgical group.

Ductal carcinoma in-situ is also referred to as noninvasive, or Stage 0 breast cancer. It is primarily diagnosed by screening mammogram, as it often does not form a palpable lump. DCIS accounts for approximately 20% of all breast cancers detected by mammography. As screening mammography has become more prevalent, the rate of DCIS detection has increased. Since DCIS does not always progress to invasive cancer, it is a very reasonable for a newly diagnosed woman to ask “Do I need surgery?”.

A hallmark of cancer is the ability to invade surrounding organs and metastasize, and whether or not DCIS should even be considered “cancer” has been the subject of much debate. Dr. Laura Esserman and others have suggested that DCIS be re-classified as an Indolent Lesion of Epithelial Origin(2). The traditional therapy for DCIS is surgical excision (lumpectomy or mastectomy depending on the extent of disease), radiation therapy, and hormonal therapy such as tamoxifen if the DCIS is estrogen receptor positive. The concern of Dr. Esserman and many others is that we are overdiagnosing and overtreating many women. It is estimated that approximately 25-50% of cases of DCIS will likely progress to invasive disease – 60% over 10 years for high grade vs 16% for low grade (1). Preventing invasive disease, which carries a possibility for metastasis, is the primary goal when treating DCIS.

Unfortunately, we are not yet in a position to accurately predict which cases of DCIS will progress and which will not. The study by Sagara et al categorized the DCIS by tumor grade, and this is an important factor in predicting biologic behavior. However, as was pointed out by Margenthaler and Vaughan in their commentary No Surgery for Low Grade Ductal Carcinoma In Situ? (3), a detailed tumor genomic analysis such as the 12-gene assay provides more comprehensive information about tumor behavior and prognosis. Currently this assay is being used in selected cases to classify DCIS as low, intermediate and high risk and to guide treatment. Another limitation of the Sagara study is the retrospective nature, so that information regarding surgical margins and other factors known to be important in recurrence rates is not known. In addition, only 2% of the patients with DCIS underwent non-operative therapy, so the sample size is very small. It is also not known why some women did not undergo surgery.

An additional concern regarding nonoperative therapy is that if surgery is not performed, the diagnosis depends on the accuracy of the core biopsy. In approximately 15-20% of cases when DCIS is found on core biopsy, the surgical pathology actually demonstrates invasive cancer (4). As the entire lesion cannot be sampled with needle biopsy, we don’t know if we are actually observing an invasive cancer.

So can surgery be avoided in women with early stage breast cancer? My answer is in selected cases possibly, but more information is needed. Several ongoing trials will hopefully provide some answers. In the United States, the ALLIANCE trial involves treating patients with letrozole for 3-6 months prior to surgery with tumor assessment by biopsy and MRI. A similar study is being performed at the University of California San Francisco using either tamoxifen or letrozole prior to surgery. Both studies are evaluating tumor biomarkers to help determine if response can be predicted based on specific tumor factors.

In Europe, 2 non-operative trials are opening – LORD and LORIS. Both will include patients with low-grade DCIS and randomize them to either active surveillance or treatment.

We are anxiously awaiting the results of these studies. Identifying women who do not benefit from treatment is an important question that needs to be answered. However at this time, we do not have enough information to make the general recommendation of active surveillance for all women with low grade DCIS.

References:
1. Sagara Y, et al. Survival Benefit of Breast Surgery for Low Grade Ductal Carcinoma In Situ: A Population-Based Cohort Study. JAMA Surg Published online June 03, 2015.;():. doi:10.1001/jamasurg.2015.0895.
2. Esserman LJ, et al. Overdiagnosis and Overtreatment in Cancer: An Opportunity for Improvement. JAMA 2013:310(8)797-798
3. Margenthaler JA, Vaughan A. No Surgery For Low-Grade Ductal Carcinoma In Situ? JAMA Surg Published online June 03, 2015. doi:10.1001/jamasurg.2015.0895
4. Kumiawan ED et al. Risk Factors for Invasive Breast Cancer when Core Needle Biopsy Shows Ductal Carcinoma In Situ.
Arch Surg 2010;145(11)1098-1104

28 January 2015

A study published in the journal Cancer found that many women lack basic knowledge about their breast cancer. Researchers at the Dana Farber Cancer Institute in Boston surveyed 500 women treated between 2010-2011 for Stage 0 – III breast cancer in Northern California. Women were asked about 4 tumor characteristics – estrogen receptor (ER) status, Her2/neu status, tumor grade and disease stage.

They found that overall, 55% reported knowing their ER status, 33% reported knowing their Her2/neu status, 82% reported knowing their disease stage, and 32% reported knowing their tumor grade. 14% reported knowing all characteristics, and 14% reported knowing none.

However, patient perception of knowledge did not reflect actual knowledge. Only 8% answered all questions correctly. They also found that African American and Hispanic women had a lower rate of stated knowledge and correct answers. Differences in education and health literacy were associated with less knowledge about one’s own condition, but controlling for these factors did not eliminate the observed differences for minority participants.

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The findings are important for several reasons. As the authors noted in their manuscript, “having knowledge about one’s health conditions or the risk of developing health conditions can promote healthy behaviors and treatment adherence. Better general knowledge about cancer is associated with cancer screening, earlier stage at presentation and survival, and enhanced satisfaction with care.” “Improving a patient’s understanding about why a particular treatment is important to her individual situation may lead to more informed decisions and better adherence to treatment plans.”

While it is generally felt that breast cancer patients are highly educated about their disease, this study shows that as physicians, we have a long way to go. We need to do a better job assessing a patient’s understanding of their disease and treatment options, and we need to design and participate in research studies that evaluate new and innovative ways to explain complicated information to a newly diagnosed breast cancer patient taking into account education level as well as racial, ethnic and cultural differences. Our discussions need to be tailored to the individual patient. And patients should feel empowered to ask questions and obtain clarification in order to fully understand the treatment recommendations and the rational behind those recommendations.

Reuters News Coverage