15 March 2020

Ductal carcinoma in-situ, also known as DCIS or stage 0 breast cancer, is traditionally treated with surgical excision (lumpectomy or mastectomy). Treatment may also include radiation therapy, as well as endocrine therapy (tamoxifen or an aromatase inhibitor) if the disease is estrogen receptor positive (ER+).

For invasive cancer, we sometimes take a neoadjuvant approach, treating with chemotherapy or endocrine therapy prior to surgery. This has the advantage of confirming that the tumor will actually respond to treatment. In addition, in cases where the tumor does not completely resolve with treatment (based on pathology assessment of the tissue that is removed), additional chemotherapy or targeted treatments may be recommended.

We have not traditionally used a neoadjuvant approach for DCIS. While invasive cancers may shrink in response to treatment, it is unclear if that reliably happens with DCIS. A study recently published used letrozole (Femara – an aromatase inhibitor) in patients with ER+ DCIS. Patients were treated for 6 months, had MRIs at baseline, 3 and 6 months, and then underwent surgery. The size of abnormality on MRI (which often, but not always correlates with the amount of disease) was measured, and ER, PR (progesterone receptor) and Ki67 (a measure of cellular proliferative activity) was assessed on the pre-treatment needle biopsy and on the surgical specimen. 79 patients were enrolled, 70 completed 6 months of letrozole, and MRI data for all 3 time points was available for 67 patients.

The study found that:

  • Median volume of disease as measured by MRI declined by 0.8cm 
  • ER and PR H-scores decreased by a median of 15 and 85 points, respectively
  • Ki67 decreased by a median of 6.3%

Of the 59 patients who underwent surgery, findings included:

  • Persistence of residual disease in 50 patients (85%)
  • Invasive cancer in 6 patients (10%)
  • No residual DCIS and no invasive cancer found in 9 patients (15%)

As mentioned above, the finding of residual disease is not unexpected. DCIS does not often resolve after neoadjuvant therapy, and endocrine therapy works very slowly. In addition, several patients were found to have invasive cancer – the authors suspect that most likely this was not picked up on the initial biopsy as we know the “upstaging” rate for DCIS at surgery can approach 25%. However, despite these limitations, the finding of decreased volume of disease by MRI and changes in biomarkers (ER, PR and Ki67) indicate treatment response and suggest that extended neoadjuvant endocrine therapy may eventually play a role in the treatment of ER+ DCIS and may possible replace surgery in selected patients. This was a relatively small Phase II trial, so more study certainly is needed. 

*If you are not able to access the full study and would like a copy, please email me: contact at drattai dot com

13 May 2019

Note – the survey closed on July 7th 2019. Thank you to all who participated and shared, and we will be sure to post the results when they are available!

Approximately 25-30% of patients with breast cancer who are prescribed endocrine therapy do not complete the full course of treatment, and some patients never start. Side effects of endocrine therapy are well documented but there is very little literature on the role of the medical team in helping patients manage treatment-related side effects. 

This survey is being conducted for research purposes. It is a UCLA research survey, open to women and men with a history of breast cancer who have been treated with or who have received a recommendation for endocrine therapy. 

This survey is voluntary and is completely anonymous – no identifying information, including internet protocol (IP) addresses, will be collected. The survey should take approximately 15 minutes to complete. We value your time and your opinions. 

For questions regarding this study, you may contact principal investigator Dr. Deanna Attai By phone: (818) 333-2555; by email: [email protected]; or by mail: 191 S. Buena Vista #415, Burbank, CA 91505

UCLA Office of the Human Research Protection Program (OHRPP):
If you have questions about your rights as a research subject, or if you have concerns or suggestions and you want to talk to someone other than the researchers, you may contact the UCLA OHRPP  By phone: (310) 206-2040; by email: [email protected]; or by mail: Box 951406, Los Angeles, CA  90095-1406

Research Survey Link

6 March 2019

The American Society of Breast Surgeons (ASBrS) held their annual meeting in Dallas last week. This meeting usually draws about 1500 breast surgeons (just under half the ASBrS membership) from around the world, for several days of pre-meeting courses, didactic sessions, and research presentations. In addition to the science, the meeting provides opportunities for breast surgeons in all types of practice settings and at all levels of training and practice to network and learn from each other. 

The following covers some highlights from the general session. 

The meeting started off with the Critical Issues in Breast Cancer Forum: Changing Paradigms for Breast Cancer Surgery. Dr. Cary Kaufman presented an update on current clinical trials for cryoablation for breast cancer. Cryoablation is a technique that freezes the tumor, using a small probe placed into the tumor (similar to a needle biopsy) under local anesthesia. There are several types of ablative therapy including laser, radiofrequency, high-frequency ultrasound, and cryoablation. Because cold is a natural anesthetic agent, patients undergoing cryoablation do not need any sedation, and the procedure is performed while they are awake. 

Cryoablation was initially tried with benign tumors (fibroadenomas). In many cases, the fibroadenoma reabsorbed, leaving no mass and only a tiny (3 millimeter) scar. Multiple studies have looked at the use of cryoablation for breast cancer, and most have restricted therapy to patients with small (1.5 cm or smaller) estrogen receptor positive, Her2/neu negative tumors. I participated in a national multi-center trial, the ACOSOG / ALLIANCE Z1072 trial, which was published in 2016 and demonstrated that cryoablation was successful in the majority of these patients. All patients in the ACOSOG / ALLIANCE Z1072 study underwent surgery within one month of the ablation, so that the tumor site could be removed and evaluated. Several subsequent studies have looked at cryoablation for breast cancer without surgery. The longest follow up was from Dr. Fukuma in Japan. After 12 years of follow up, he reported 3 local (in-breast) recurrences in 304 patients. Combining 3 published trials, Dr. Kaufman noted that local recurrence rates range from 0.98 – 1.4%, and he concluded that this is extremely promising technology. He also noted that cryoablation of breast cancer appears to have an immunologic benefit – when the tumor cell membranes are disrupted by the extreme cold, the patient is exposed to tumor antigens, which may prompt antibody formation. It is very premature to determine if this immunologic effect will help reduce recurrence rates.

Dr. William Small presented updates on 3 clinical trials of intraoperative radiation therapy (IORT). An advantage of IORT is that it is delivered at the time of lumpectomy, in the operating room, as a one-time treatment. A disadvantage is that status of the lumpectomy specimen margin and lymph nodes are not known at that time. If it is found on final pathology that there are positive margins, external beam radiation is recommended, and at least one trial noted that approximately 30% of patients who received IORT required additional whole breast radiation. Most studies of IORT have been limited to “low risk” lesions – small, low grade invasive cancers in older women. He discussed that a criticism of these studies is that some of these women may not have needed radiation therapy at all. Dr. Small noted that local recurrence rates are slightly higher (3.3 versus 1.3%) but that statistically, IORT is considered “non-inferior” to whole breast irradiation. He noted that seroma (fluid accumulation) is more common in patients who undergo IORT.  He concluded by stating that there is an “acceptable” toxicity, with non-inferior local recurrence. However, as there is relatively short follow up available in low risk patients, he questioned the applicability of this procedure to a broader patient population. A US registry is planned.

Dr. Antonio Toesca presented the results of his study of 100 patients who underwent robotic nipple sparing mastectomy (NSM) and implant reconstruction, and showed a fascinating video which highlighted the precise and meticulous dissection, along with improved visualization, compared to a standard surgical procedure. The average incision size was a little over 1 inch, and the specimen was removed intact (in one piece). The procedure averaged 1 hour and 18 minutes longer than their standard for a nipple sparing mastectomy and implant reconstruction (3 hours, 36 minutes for the robotic procedure. Patients who underwent the robotic procedure were less likely to have axillary web syndrome and reported Improved physical, psychological and sexual well-being. 

Why could performance of NSM using robotic technology become important? Dr. Tina Hieken presented the results of her study (abstract 580759, page 31) showing that as experience with the procedure has grown, indications are expanding and patients who previously were not candidates for the procedure are now being considered. A NSM is a technically challenging procedure, and it takes a toll on the neck and back of a surgeon. A 2017 study published in JAMA Surgery noted a high incidence of work-related musculoskeletal disorders among surgeons and interventionists. Dr. Katherine Kopkash presented her research (abstract 51837, page 52) using intraoperative electromyography (EMG) on the surgeon to assess muscle strain during NSM. Of course, oncologic safety is the primary concern, and more study on the long-term outcomes (as well as costs) of robotic procedures is required. 

The next session was Emerging Strategies in Breast Cancer Care, which focused on “de-escalation” of surgical therapy. Dr. Anna Weiss provided an update of clinical trials evaluating active surveillance for low-risk ductal carcinoma in-situ (DCIS): COMET, LORD and LORIS. Approximately 60,000 cases of DCIS are diagnosed annually. Patients undergoing active surveillance do not have surgery, some are treated with endocrine therapy, and all undergo regular monitoring. This is a accepted option in select cases of prostate cancer, and Dr. Weiss noted that there is no difference in overall survival in patients with low-grade DCIS who do not undergo treatment. The LORD and LORIS trials are open in the UK and the COMET study is open in the US. (Additional perspective)

Dr. Henry Kuerer presented his research on the percutaneous management of breast cancer in the setting of a pathology complete response (pCR) following neoaduvant (before surgery) chemotherapy. He noted that for survival and recurrence matter most, but side effects and complications are significant concerns for both patients and physicians. I’ve recently covered details of his research on this blog

Some of the twitter conversation related to this talk included patients who noted that they would rather undergo surgery than chemotherapy. It is important to note that the patients involved in this study are those who were going to be treated with chemotherapy regardless of surgical therapy because they have triple negative or Her2/neu positive breast cancer. In these patients, systemic (whole-body) therapy is necessary due to the higher likelihood of metastatic disease. Surgical therapy in these patients, especially the “exceptional responders”, may not improve outcomes, but of course more study is needed. Surgery remains the standard of care for breast cancer therapy.

Dr. Judy Boughey discussed several cooperative group trials evaluating management of the axillary (underarm) lymph nodes, and these studies are also focusing on how we can safely de-escalate axillary surgical therapy after neoadjuvant chemotherapy. This is an area that is rapidly evolving with expansion of the criteria for a less aggressive approach to the axilla.

In a session on Evidence-Based Prevention and Management of Surgical Complications, Dr. Suzanne Klimberg presented on chronic post-mastectomy seroma. A seroma is a fluid collection – fluid normally accumulates after mastectomy which is why drainage tubes are left in place. Normally, drains can be removed after 7-14 days, but about 30% of patients will develop prolonged drainage. This is a frustrating problem for patients and physicians as the persistent fluid can be uncomfortable, may increase the risk of infection, and may delay the start of planned chemotherapy or radiation. She noted that a surgical technique to close the tissue known as “quilting” can reduce the rate of chronic seroma, but that it results in excessive skin dimpling and has a significant impact on the cosmetic results. She stated that additional drainage tubes, various “sealant” agents and compression (such as wearing an ace wrap) are not effective. The area may be sclerosed (scarred) by instilling talc or antibiotics, and in some cases, re-operation to remove the inflamed tissue is indicated. Otherwise she recommended patience and repeat aspirations. She noted that there are no ways to successfully prevent seromas from forming.

Dr. Amal Khoury presented on chronic post-mastectomy pain, and noted that persistent pain occurs in 25-60% of patients undergoing any type of breast surgery. It is thought that this chronic and at times severe pain is due to damage to and neuroma formation of the cutaneous (skin) branches of nerves that run along the 4thand 5thribs, which are roughly at the inframammary fold (bra line below the breast). These cutaneous nerve branches are often not visible at the time of surgery. She noted that the pain syndrome it is often not recognized, and when recognized it is often not treated effectively. She stated that injections with a combination of long-acting local anesthetic and steroid (in a very small dose) at the trigger points is more effective than taking pain or other medications, and in their study at UCSF, 91% of patients required only one injection for lasting relief.

The next session was Practical Considerations for Systemic Treatment. Dr. Judy Boughey reviewed the I-SPY2 clinical trials, which utilize an innovative “adaptive randomization” approach in patients who are undergoing neoadjuvant chemotherapy for triple negative, Her2/neu positive, or other high risk breast cancers. pCR rates are assessed, and drugs that are successful move up higher in the randomization algorithm. This study and its flexible randomization protocol have accelerated the use of some novel agents. Patient reported outcomes assessing quality of life, fear of recurrence, symptoms and side effects are being assessed. If drug response rates are similar, the “winner” may be the one associated with fewer side effects. Dr. Barry Rosen discussed specific strategies to identify the previously involved axillary lymph nodes when chemotherapy is performed prior to surgery. Dr. Elizabeth Mittendorf presented on breast cancer immunotherapy and surgical implications of these treatments. She noted that one agent, atezolizumab, is currently approved for use in patients with metastatic triple negative breast cancer. She noted that there are concerns about wound healing complications with these agents but unfortunately the clinical trials did not specifically assess for this. In addition, she noted that some immunotherapy agents are associated with development of adrenal insufficiency – this complication has only been reported in a small percentage of patients, but it is an important consideration in any patient who is going to have surgery.

A session was held on breast imaging. Dr. Molly Sebastian presented on the impact of breast density on breast cancer risk, noting that it is more difficult to screen patients with dense breasts, and that these patients are also at increased risk for developing breast cancer. The associated breast cancer risk increases with the level of density. Approximately 50% of women in US are considered to have dense breast by mammogram, and she cited a 2010 study that found that 30% of breast cancers could be linked to highly dense breast tissue. Contributors to increased density include younger age, use of hormone replacement therapy, race (Asian), diet (Western), alcohol use, and hereditary factors. She did stress that the presence of a germline genetic mutation (such as BRCA 1/2) conveys a much higher level of risk (regardless of density) than breast density itself. 

Dr. Brigid Killelea discussed balancing high-risk screening (which usually includes MRI) with the concerns about gadolinium toxicity. Gadolinium is a “rare earth heavy metal”, and is used in the contrast material that is administered (using an intravenous line) when breast MRI is performed. Acute allergic reactions are uncommon but as gadolinium is excreted through the kidneys, there are concerns about the potential for kidney damage especially in patients with pre-existing renal insufficiency. Nephrogenic systemic fibrosis (NSF) is an unusual condition that results in progressive deposition of gadolinium in the skin. It has also been found that the number of exposures to the linear form of gadolinium (as opposed to macrocyclic, which is what is most commonly used with breast MRI) correlates with increasing deposits in the brain. More research is needed to determine if this leads to an increased risk of Parkinson’s or other diseases. Studies evaluating “fast” MRI protocols are ongoing but they still use gadolinium contrast. Some work is being done with non-contrast MRI and Dr. Killelea noted that it shows some promise in detecting certain lesions. 

In the session on Ethical Issues in Breast Cancer Surgery, Dr. Rachel Greenup discussed how to manage the situation when the principles of respect for patient autonomy conflict with the standard of care. She noted that patient autonomy allows for us (as physicians) to educate but not to decide care for patients, and that poor physician-patient communication is a key factor in patients opting for non-standard care. Factors associated with patients declining standard therapy include a negative first experience, an uncaring / insensitive / unnecessarily harsh oncologist, fear of side effects, and belief in the efficacy of alternative therapy.  In regards to endocrine therapy for breast cancer, she noted that unmanaged side effects are a significant contributor to stopping therapy. She also presented data showing poorer outcomes in patients who declined standard therapy, and that many, when faced with disease progression, did then opt for conventional treatment. She recommended that physicians review and present evidence to their patients in an understandable way, taking time to acknowledge fears and address patient barriers to treatment, provide time to adjust to diagnosis, suggest a 2ndopinion, and avoid abandonment or fear tactics. She also suggested that physicians be more open (when medically safe) to the combination of alternative and standard therapy. She stressed that patient autonomy is the priority, and that open communication can help align patient-centered care with evidence-based care. 

Dr. Terry Sarantou discussed the ethical issues of obtaining informed consent when performing a new surgical procedure, noting that there is FDA oversight for new drugs and surgical devices, but not for surgical procedures. He stressed that informed consent is a communication process, not a form to be signed. 

Recognizing the role that surgeons play in the current opioid crisis, Dr. Sarah DeSnyder discussed proper prescribing of narcotics in breast surgery. There was also an abstract presentation by Dr. Betty Fan (abstract 5808940, page 27) on this subject. She noted that women who expected postoperative pain or those who reported higher preoperative distress used more postoperative opioids for pain management. She stressed that physician and trainee education about proper prescribing is critical as is setting patient expectations for postoperative pain and providing non-narcotic options. The use of nerve blocks, long-acting local anesthetic agents, acetaminophen (Tylenol) and ibuprofen were also discussed. 

Photographs are an important part of breast and reconstructive surgery to document results both for patient and physician education as well as for quality assurance, and Dr. Toan Nguyen reviewed some of the ethical, legal and technical considerations to protect patient confidentiality and privacy. The ASBrS statement on this issue has been published in the Annals of Surgical Oncology.

In the session covering New Perspectives on Old Problems, Dr. Lee Wilke noted that with improved surgical techniques, breast conservation is now appropriate for select patients with more than one tumor in the breast. She did note that in up to 20-30% of patients with more than one tumor in the breast, the tumors are different subtypes, which may have implications for therapy – so pathologic analysis needs to be performed on all lesions. Dr. Stephen Grobmyer reviewed the current literature on local (in-breast) recurrence, noting that repeat breast conservation may be appropriate in some patients. However, if repeat radiation is performed, there is a higher risk of skin toxicity and potentially unacceptable cosmetic results. In addition, for left-sided breast cancers, repeat radiation raises concerns about cumulative radiation damage to the heart. Repeat lumpectomy without radiation is associated with a 20-40% risk of local recurrence. IORT may be utilized in some patients, but studies are ongoing and data is limited.

Dr. David Euhus discussed that genetic testing does not only potentially impact the surgical procedure that is recommended, but may influence the decision for radiation therapy as well as systemic therapy. In addition, results of genetic testing may impact surveillance for additional breast or other cancers in the patient as well as recommendations for family members. The ASBrS recently updated their genetic testing guideline, recommending that genetic testing be considered for newly diagnosed breast cancer patients. (Additional perspective)

In the session on Benign Breast Disease, Dr. Jane Mendez reviewed breast fistulas (persistent drainage through the skin) and infections, and Dr. Vincent Reid reviewed some of the non-malignant masses that can develop in the male breast. Dr. Katrina Mitchell, who is a breast surgeon as well as a certified lactation consultant, provided recommendations for management of post-partum patients who develop mastitis or breast abscess. One of the key recommendations was that patients should continue breast feeding (better than pumping for keeping the breast empty) and that patients do not need to “pump and dump” the milk while on antibiotics. 

Dr. Stephanie Valente discussed breast pain, which is a common problem that frustrates both patients and physicians. Pain is a symptom of breast cancer in less than 2% of cases.  Suggestions for treatment include decrease caffeine, nicotine, and dietary fat intake, and consider supplementation with essential fatty acids such as evening primrose oil (EPO) or vitamin E. However, she noted that that some studies show that EPO and vitamin E are no better than placebo. Both flaxseed and chasteberry have shown to be effective. Diclofenac (a non-narcotic pain medication) gel can be effective but it needs to be used for several weeks before improvement is seen and it is expensive. In severe cases, danazol (an androgen hormone) or tamoxifen can be used but are associated with significant side effects.

There were several sessions on oncoplastic surgery. Oncoplastics refers to combining oncologic (cancer) surgery with attention to cosmetic outcomes. Basic principles include placing the incision in the least conspicuous place and closure of as much of the breast tissue once the tumor has been removed as possible to minimize, or preferably avoid, a depression in the area. More advanced techniques include rotation flaps and mastopexy (lift) that may be performed by breast surgeons or breast surgeons collaborating with their plastic surgical colleagues. There was also a session discussing some of the advanced microvascular procedures that are being studied to treat lymphedema as well as a video session showing some basic techniques to perform a better (flat) closure for patients undergoing mastectomy without reconstruction. 

The keynote address was delivered by the actress Kathy Bates. Ms. Bates underwent a bilateral mastectomy for breast cancer and has bilateral arm lymphedema. She is a spokeswoman for the Lymphatic Education and Research Network, working to educate, support, and advocate for patients who have lymphedema. She delivered a moving and unique address to the group, combining science and her personal patient perspective. An abstract (abstract 581304, page 22) presented during the meeting demonstrated that postoperative surveillance with bioimpedence spectroscopy compared to tape measure resulted in a 10% decrease in the number of patients requiring complex decongestive physiotherapy. However, these results, which were a planned interim data analysis, did not reach statistical significance.

The new ASBrS screening mammography guidelines were released at the meeting. They recommend formal risk assessment starting at age 25 and a risk-based approach to screening, as well as annual mammography starting at age 40 for average-risk women. (Additional commentary)

All of the research abstracts and posters can be found here. There were many interesting and thought-providing presentations, but it is important to remember that abstracts represent incomplete data and have not been subject to the peer-review process. The oral abstracts that were presented will be published in manuscript form later this year. The poster gallery can be found here (not all posters have been uploaded by the presenters).

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

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

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

15 August 2016

A consensus statement was released today by the Society of Surgical Oncology, the American Society for Radiation Oncology, and the American Society of Clinical Oncology. It addresses the issue of surgical margins for patients undergoing breast conserving surgery (lumpectomy) for ductal carcinoma in-situ (DCIS). The summary notes “Use of a 2-mm margin as the standard for an adequate margin in DCIS treated with whole-breast irradiation is associated with lower rates of IBTR [in-breast tumor recurrence, also known as local recurrence] and has the potential to decrease re-excision rates, improve cosmetic outcomes, and decrease health care costs. Clinical judgment should be used in determining the need for further surgery in patients with negative margins narrower than 2 mm.”

We know from many years of research that women who undergo lumpectomy have the same survival rates as those who undergo complete breast removal. When a lumpectomy is performed, the goal is to remove the tumor with a rim of normal breast tissue (margin). It has long been debated how much margin is needed. If clear margins are not obtained, repeat surgery is usually recommended, and due to lack of standardized guidelines, re-excision has been recommended for many patients with close margins. Nationally re-excision rates have been reported as high as 50%. Additional surgery increases the likelihood of complications, increases overall breast cancer treatment time, and may have a negative impact on cosmetic results.

In 2014, margin guidelines were published for invasive breast cancer, and they noted that for patients with early stage breast cancer undergoing lumpectomy and radiation therapy, “no ink on tumor” is an acceptable margin. Today’s DCIS statement notes that a 2mm margin is acceptable in most cases of non-invasive cancer. Why the discrepancy? Shouldn’t invasive cancer be treated with a wider margin than DCIS? An important distinction between invasive cancer and DCIS is that DCIS lesions are more likely to have “skip areas”, so a clear margin may not be as predictive of a low likelihood of residual disease. However, just as with the invasive cancer guidelines, the current consensus guideline notes that wider margins do not improve outcomes.

Both the invasive and DCIS statements apply to patients with stage I and II breast cancer, undergoing lumpectomy with postoperative radiation therapy. Without radiation therapy, the risk of local recurrence (the same cancer returning in the breast) can be as high as 30-40%. However, there are certain situations when radiation therapy may not be recommended, depending on tumor type, patient age, and other factors.

As with other clinical practice guidelines, the current statement is not a substitute for good clinical judgement and multidisciplinary case discussion. There are situations when a smaller margin may be acceptable, and settings where a larger margin may be desired for various reasons. However, patients and physicians need to be aware that more surgery is not better when it comes to breast cancer treatment. Dr. Monica Morrow, lead author on the statement, advised that “if a woman with a negative margin is told to have a re-excision, she needs to ask what factors are prompting the surgeon to recommend that re-excision.”

An Oklahoma mayor underwent a 3D mammogram (tomosynthesis) as part of a hospital promotion. She was diagnosed with ductal carcinoma in-situ (DCIS, also known as Stage 0 breast cancer) and she stated that the study “…saved my life.” She also recommended that women make sure to obtain a 3D mammogram. The story noted that tomosynthesis “virtually eliminates” the need for additional testing, and that early detection makes it less likely that the patient will need to undergo chemotherapy or radiation.

Here are a few errors in the story:

Statement: the mammogram saved my life
Fact: survival from breast cancer depends on many factors. The survival rate for patients with DCIS, regardless of treatment, is close to 97%. For invasive cancers, survival rates depend on stage as well as tumor biology. Small breast cancers “caught early” can still be lethal. It’s not the cancer in the breast that kills, it’s the cancer that gets to other areas of the body. Small tumors can and do spread.

Statement: early detection makes it less likely that a patient will need chemotherapy
Fact: the need for chemotherapy depends on tumor stage as well as tumor biology. As noted above, some very small, early stage breast cancers are very aggressive and have a high likelihood of spread, so chemotherapy is recommended. This is especially true for “triple negative” and “Her2/neu over-expressed” breast cancer subtypes.

Statement: early detection makes it less likely that a patient will need radiation therapy
Fact: radiation therapy is a standard recommendation for women with early stage breast cancer who undergo a lumpectomy. Since most women with early stage breast cancer are candidates for a lumpectomy, this statement simply doesn’t make any sense.

Statement: tomosynthesis “virtually eliminates” the need for additional imaging
Fact: while tomosynthesis can reduce the likelihood of needing additional views (“callback”) especially in women with dense breast tissue, diagnostic imaging with possible biopsy are still recommended when a concerning abnormality is seen.

While I certainly wish Ms. Noble well, stories like this always make me cringe, because they over-simplify a very complex situation. Here are some posts from Health News Review with some additional information:
Mayor: 3D Mammogram Saved My Life
3D Mammography and False Hope

 

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.

 

14 October 2015

The discussion on whether or not DCIS is cancer, and how best to treat it, continues.

A study published recently in the Journal of Clinical Oncology by Dr. Lawrence Solin and colleagues evaluated the risk of developing an invasive cancer if radiation therapy was not performed after lumpectomy for DCIS. This was a prospective non-randomized trial. Patients were enrolled from 1997 – 2002. Patients were divided into 2 groups: 1.) low or intermediate grade DCIS, tumor size 2.5cm or smaller (561 patients), and 2.) high-grade DCIS, tumor size 1cm or smaller (104 patients). All patients underwent lumpectomy but none received radiation therapy.

The study reports 12 year results. There were 99 “in-breast events” (IBE – a new DCIS or invasive cancer), 51 (52%) were invasive. The rates of all IBE and invasive IBE continued to increase during the surveillance period. The 12 year rates of developing an IBE were 14.4% for the low-risk group and 24.6% for the high-risk group. The 12 year rates of developing an invasive IBE were 7.5% for the low-risk group and 14.3% for the high-risk group. In addition to low or high-risk category, tumor size was correlated with risk of recurrence. Patient age, menopausal status, size of surgical margin, use of tamoxifen, or prior use of hormone replacement therapy were not associated with risk of developing an IBE.

The authors concluded that “individual patients and their physicians will need to decide if these 12-year risks are acceptable, and to judge whether or not to add adjuvant treatment [radiation and/or hormonal therapy such as tamoxifen] after surgical excision. Not all patients and their physicians will agree on what is considered too high a risk of developing an IBE or an invasive IBE to recommend observation after surgical excision, or what risk is considered too low to justify adding radiation treatment.” While this may lead to more confusion on the part of patients, it points out the need for careful discussion of the risks and benefits of treatment and observation, as well as an assessment of an individual’s risk tolerance.

Adding to the DCIS discussion, was an abstract presented at the 2015 American Society of Clinical Oncology Breast Cancer Symposium. Dr. Kimberly VanZee and colleagues presented an abstract on recurrence rates of DCIS. They retrospectively reviewed a database of DCIS cases between 1978 – 2010 at the Memorial Sloan Kettering Cancer Center in New York. There were 363 (12%) recurrences in 2996 cases. The 5-year recurrence rate from 1978 – 1998 was 13.6% versus 6.6% between 1999 – 2010. Interestingly, the decrease in recurrence rates were limited to patients who did not undergo postoperative radiation therapy. There was no decline in recurrence rates during the 2 time periods in patients who received radiation therapy. They concluded that the rates of recurrence after treatment for DCIS are declining over time, possibly due to improvements in detection and pathologic assessment. The authors felt that it was important to stress to women with DCIS that are considering mastectomy, that while recurrence is a possibility after treatment for DCIS, the rates are very low. This was presented as an abstract and not a full manuscript – I am looking forward to more detailed analysis and discussion when the full paper is published.

The Breast Cancer Symposium also featured a pro-con debate between Dr. Ben Smith (radiation oncologist from MD Anderson) and Dr. Shelley Hwang (surgical oncologist from Duke University). The topic – “Is DCIS Cancer?”. Dr. Smith took the pro / yes position, and Dr. Hwang took the con / no position. Both gave excellent presentations, citing compelling studies and statistics. They both gave a similar analogy, presenting progression of DCIS to invasive cancer as a “crime”. Dr. Smith took the position of wanting to stop the crime before it happened:

While Dr. Hwang noted “should everyone be punished as if they would commit a crime?”

It was definitely an entertaining and spirited debate, but unfortunately we still don’t have the answers for an individual patient faced with this diagnosis.

This isn’t just a discussion that breast cancer specialists are having. A TIME Magazine story: Why Doctors are Re-Thinking Breast Cancer Treatment also addressed the concerns about over-diagnosis and over-treatment, especially for low-grade DCIS. I think the story did a good job covering the controversy over screening mammograms and it raised some good points about cancer treatment and medical progress. It’s worth a read.

NPR discussed a study recently published in the Journal of the National Cancer Institute – Trends in Treatment Patterns and Outcomes for Ductal Carcinoma In-Situ. This was a study using the SEER Registry. 128,080 patients treated for DCIS between 1991-2010. They found that over time, the number of women treated by lumpectomy and radiation increased, while the number of women treated by mastectomy decreased. However, there was an increase in the rate of bilateral mastectomy for DCIS – 0% in 1991 and 8.5% in 2010. The rate of women opting for no treatment increased from 1% to 3% during the study period.

Overall survival was 89.6% in women who underwent lumpectomy and radiation, 86% for those who underwent mastectomy, and 80% for those who underwent a lumpectomy without radiation. However, only 9% of overall deaths were due to breast cancer – the majority of deaths were due to cardiovascular disease. It is well known that more women in this country die due to cardiovascular disease than from breast cancer. Deaths specifically from breast cancer (more relevant than overall survival) were identical for the lumpectomy-radiation, mastectomy, and lumpectomy alone groups. This again raises the need for additional research into which women will truly benefit from treatment for DCIS.

And finally (for now, anyway), Dr. Laura Esserman and others were quoted in an ASCO Post article: Where We Have Been and Where We Can Be. The authors elaborated on points that were made in an August 2015 JAMA Oncology editorial: Re-Thinking the Standard for Ductal Carcinoma In-Situ Treatment. The authors suggested that radiation therapy not be routinely recommended after lumpectomy when the DCIS is not high-grade, as there has been no demonstrated survival advantage. They also suggested that low- and intermediate-grade DCIS should not be a target of screening and early detection. They noted significant challenges in abandoning the use of radiation and decreasing the number of biopsies performed for calcifications that likely represent low grade disease. They also called for more research to be performed to understand the biology of the highest-risk lesions and patient populations.

To be continued…

24 August 2015

A study published in JAMA Oncology raises more questions regarding appropriate treatments for ductal carcinoma in-situ (DCIS). I wrote about surgery for DCIS about a month ago. The controversy continues.

The JAMA Oncology study by Dr. Steven Narod and colleagues used the SEER Database to try to determine if treatment for DCIS improves the death rate. They found that breast cancer-specific mortality was approximately 3.3% over a 20 year period, a very low rate. Certain patient populations such as women under the age of 40, African Americans, and patients with ER-negative and more aggressive subtypes of DCIS had higher mortality rates.

This study has led to headlines including Doubt is Raised over the Value of Surgery for Breast Lesion at Earliest Stage (New York Times, New Breast Cancer Study Raises Questions, Delivers Few Answers (NBC News), Study Sparks Debate on Treatment for Early Stage Breast Cancer (USA Today) and Early Stage Breast Cancer Not a Death Sentence (WebMD). Evaluation of the news coverage by Health News Review provided some context. Linked below are the comments of several experts.

The scope of the problem is huge. DCIS represents approximately 20-25% of all breast cancers, and about 60,000 women in the US will be diagnosed every year. It is most commonly diagnosed by mammography, as it usually does not form a lump. DCIS is known as “Stage 0” breast cancer – under the microscope, the cells look the same as invasive cancer cells, but they are contained within the milk ducts. DCIS has been considered a non-obligate precursor to invasive cancer (may turn into but doesn’t always). A less common point of view considers DCIS to be a “high risk” lesion indicating an increased risk of developing breast cancer in the future. Since we don’t have a good way to determine which lesions simply indicate high risk and which ones will progress, we generally recommend surgery, radiation therapy, and hormonal therapy (such as tamoxifen or aromatase inhibitors, if the DCIS is hormone-receptor positive) with the goal of reducing the risk of invasive cancer and death. The Narod study is notable in that the researchers found that regardless of whether or not women received radiation therapy, survival rates did not change. If DCIS is a direct precursor to invasive cancer, treatment that reduces recurrence rates should result in improved survival.

What is very clear is that DCIS is not one disease, and we haven’t yet gotten to the point of being able to pin this down for the individual woman. Some forms of DCIS may indeed simply be markers of increased risk. Lifestyle changes, hormonal, or immunological therapies could potentially be used to reduce the risk of invasive cancer in these cases, a point raised by Drs. Laura Esserman and Catherine Yau in their JAMA Oncology editorial: Rethinking the Standard for Ductal Carcinoma In Situ Treatment. Some women may ask, “what is the harm in treatment?” or “isn’t it better to be sure?”. But surgery, radiation therapy and hormonal therapy are associated with long term side effects such as pain, breast fibrosis and scarring, lymphedema, osteoporosis and more.

There are some limitations of the study. It was a database review, not a prospective randomized trial, which is considered the “gold standard” for research. While the researchers report on 20-year mortality rates, these are projected, not actual rates – women were followed for variable amounts of time, depending on when they were diagnosed and entered into the database. Other factors such as family history and presence or absence of a genetic mutation were not evaluated.

Research is clearly needed in multiple areas including the biologic behavior of the various subtypes of DCIS as well as racial, ethnic and age-related differences related to tumor behavior. In the meantime, women newly diagnosed should keep in mind that we do not have all the answers. A careful case-by-case evaluation is necessary to help come up with the most appropriate treatment plan, based on our current knowledge and an individual woman’s preferences. A diagnosis of DCIS is not an emergency. Take your time to become informed before making your decisions.

To be continued…

Expert Opinions:
How Should we Treat Stage 0 Breast Cancer Dr. David Gorsky
Why Women and Doctors Need to Know More About DCIS Dr. Elaine Schattner
Treatment for Early Breast Cancer will Benefit Some Dr. Otis Brawley
Are All Appearances What They Seem? New Insights into DCIS Dr. Susan Love
What the Headlines Got Wrong About The New DCIS Study Oncology Times
How Do We Treat Early Stage Breast Cancer The Diane Rehm Show (NPR) with Drs. Barnett Kramer, Shawna Willey, Vinay Prasad and Daniel Kopans