Expert Analysis Highlights:

• There is continued evidence that prophylactic removal of the breast and ovaries decreases mortality rate
• This subject is not without controversy, but results of studies have been impressive
• For example, study demonstrates removal of the ovaries in select groups of mutation carriers can cut the risk of ovarian cancer by 70%
• Visit PatientResource.net for more information about breast and ovarian cancer

For breast cancer women who carry the BRAC-I or BRAC-II mutations, there is continued evidence that prophylactic removal of the breast and ovaries decreases mortality rate.  Prophylactic removal simply refers to surgically removing the breast or ovary that is not known to contain cancer for the purpose of reducing the patient’s risk. For your reference, below are relevant summary abstracts from professional medical journals. This subject is not without controversy. Removing healthy tissue, for example the breast that may otherwise never develop cancerous cells despite having cancer in the opposite breast, is a difficult choice that’s not for everyone. Talk to your doctor about your options.

A recent report from Dr Domchek and colleagues from the University of Pennsylvania in the Journal of American Medical Association showed that prophylactic mastectomy (breast removal) and removal of the ovaries significantly reduce mortality in this select group of women. They examined the survival outcome in a group of 2,482 BRAC-I or BRAC-II mutation carriers identified at 22 medical centers in North America and Europe who were participating in the prospective clinical trial. Approximately 10% of these women underwent prophylactic mastectomies and 40% underwent prophylactic removal of their ovaries.

The results were impressive. No breast cancers developed in mutation carriers who underwent prophylactic mastectomy whereas breast cancer did develop in 7% of those who declined prophylactic mastectomy. The results were even more impressive in preventing ovarian cancer which is much more lethal at the time of diagnosis. Among women who underwent prophylactic removal of their ovaries, only 1% subsequently developed ovarian cancer and only 11% subsequently developed breast cancer. In contrast, among women who declined prophylactic removal of their ovaries, about 6% subsequently developed ovarian cancer and 19% subsequently developed breast cancer. Thus, prophylactic removal of the ovaries in this select group of mutation carriers can cut the risk of ovarian cancer by 70% in those women who did not have prior breast cancer and decrease it even further, by 85%, in those who did have prior breast cancer.

These findings illustrate why breast cancer patients may want to know about their BRCA genetic status even if they have undergone bilateral mastectomy because prophylactic removal of their ovaries, even in this group of patients, may protect them from developing a new primary malignancy. Among women with no prior breast cancer, prophylactic removal of the ovaries reduced the breast cancer by 37% in carriers of the BRCA-I mutation and by 64% in carriers of BRCA-II mutation.

Another related medical study was reported in the November, 2010 issue of the ASCO Post on women who carried the BRCA mutation. This study by Dr Metcalfe and colleagues from the University of Toronto demonstrated that women younger than 50 years with BRCA-mutated breast cancers can have a 38% risk of developing breast cancer in the opposite breast within the next 15 years. In addition, there is a 68% risk in a woman diagnosed before age 50 who chooses to keep her ovaries and has two first degree relatives diagnosed with breast cancer before the age of 50. Thus, women with a younger age at onset of their breast cancer are at significant risk for developing an opposite breast cancer or ovarian cancer during follow-up over the next 10-15 years.

The results in women who are BRCA-mutant carriers who undergo prophylactic removal of their ovaries are similar to the results reported in the previous studies.  In this circumstance the object of the study was to examine the development of opposite breast cancer in mutant carriers who had a diagnosis of cancer in the opposite breast. In this study, women who underwent prophylactic removal of their ovaries and who were younger than 50 years of age at diagnosis have a 60% risk of developing opposite breast cancer within 15 years compared to 20% of those older than 50 years of age. Women younger than 50 who underwent prophylactic removal of their ovaries had a subsequent reduction in their risk for opposite breast cancer by more than one-third. The authors concluded that “women with early-onset breast cancer have the highest risk and get the most protection from prophylactic removal of their ovaries”.

Dr. Metcalfe emphasized how these risk factors can be used in counseling women. For example, while the 15-year risk for a woman diagnosed before age 50 is 37.6% it greatly increases if she decided against prophylactic removal of their ovaries and nearly doubles if she has two or more 1^st degree relatives diagnosed with breast cancer at an early age.

KEY REFERENCES BELOW:

JAMA. 2010 Sep 1;304(9):967-75.

Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality.

Domchek SM, Friebel TM, Singer CF, Evans DG, Lynch HT, Isaacs C, Garber JE, Neuhausen SL, Matloff E, Eeles R, Pichert G, Van t’veer L, Tung N, Weitzel JN, Couch FJ, Rubinstein WS, Ganz PA, Daly MB, Olopade OI, Tomlinson G, Schildkraut J, Blum JL, Rebbeck TR.

Abramson Cancer Center and Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, USA.

Abstract

CONTEXT: Mastectomy and salpingo-oophorectomy are widely used by carriers of BRCA1 or BRCA2 mutations to reduce their risks of breast and ovarian cancer.

OBJECTIVE: To estimate risk and mortality reduction stratified by mutation and prior cancer status.

DESIGN, SETTING, AND PARTICIPANTS: Prospective, multicenter cohort study of 2482 women with BRCA1 or BRCA2 mutations ascertained between 1974 and 2008. The study was conducted at 22 clinical and research genetics centers in Europe and North America to assess the relationship of risk-reducing mastectomy or salpingo-oophorectomy with cancer outcomes. The women were followed up until the end of 2009.

MAIN OUTCOMES MEASURES: Breast and ovarian cancer risk, cancer-specific mortality, and overall mortality.

RESULTS: No breast cancers were diagnosed in the 247 women with risk-reducing mastectomy compared with 98 women of 1372 diagnosed with breast cancer who did not have risk-reducing mastectomy. Compared with women who did not undergo risk-reducing salpingo-oophorectomy, women who underwent salpingo-oophorectomy had a lower risk of ovarian cancer, including those with prior breast cancer (6% vs 1%, respectively; hazard ratio [HR], 0.14; 95% confidence interval [CI], 0.04-0.59) and those without prior breast cancer (6% vs 2%; HR, 0.28 [95% CI, 0.12-0.69]), and a lower risk of first diagnosis of breast cancer in BRCA1 mutation carriers (20% vs 14%; HR, 0.63 [95% CI, 0.41-0.96]) and BRCA2 mutation carriers (23% vs 7%; HR, 0.36 [95% CI, 0.16-0.82]). Compared with women who did not undergo risk-reducing salpingo-oophorectomy, undergoing salpingo-oophorectomy was associated with lower all-cause mortality (10% vs 3%; HR, 0.40 [95% CI, 0.26-0.61]), breast cancer-specific mortality (6% vs 2%; HR, 0.44 [95% CI, 0.26-0.76]), and ovarian cancer-specific mortality (3% vs 0.4%; HR, 0.21 [95% CI, 0.06-0.80]).

CONCLUSIONS: Among a cohort of women with BRCA1 and BRCA2 mutations, the use of risk-reducing mastectomy was associated with a lower risk of breast cancer; risk-reducing salpingo-oophorectomy was associated with a lower risk of ovarian cancer, first diagnosis of breast cancer, all-cause mortality, breast cancer-specific mortality, and ovarian cancer-specific mortality.

J Natl Cancer Inst. 2010 Nov 23. [Epub ahead of print]

Family History of Cancer and Cancer Risks in Women with BRCA1 or BRCA2 Mutations.

Metcalfe K, Lubinski J, Lynch HT, Ghadirian P, Foulkes WD, Kim-Sing C, Neuhausen S, Tung N, Rosen B, Gronwald J, Ainsworth P, Sweet K, Eisen A, Sun P, Narod SA; for the Hereditary Breast Cancer Clinical Study Group.

Affiliations of authors: Women’s College Research Institute, Toronto, ON, Canada (KM, PS, SAN); Lawrence S. Bloomberg Faculty of Nursing, University of Toronto, Toronto, ON, Canada (KM); Center for Hereditary Breast Cancers, Pomeranian Medical University, Szczecin, Poland (JL, JG); Department of Preventive Medicine and Public Health, Creighton University School of Medicine, Omaha, NE (HTL); Department of Cancer Genetics, Department of Medicine, and Department of Genetics, Epidemiology Research Unit, CHUM Hôtel-Dieu, University of Montreal, Montreal, QC, Canada (PG); Department of Genetics and Department of Medical Oncology, McGill University, Montreal, QC, Canada (WDF); BC Cancer Agency, Vancouver; BC, Canada (CK-S); Department of Population Sciences, City of Hope, Duarte, CA (SN); Beth Israel Deaconess Hospital, Boston, MA (NT); Department of Gynecology Oncology, University Health Network, University of Toronto, Toronto, ON, Canada (BR); London Regional Cancer Program, London, ON, Canada (PA); Department of Medical Genetics, Ohio State University, Columbus, OH (KS); Sunnybrook Regional Cancer Centre, Department of Medical Oncology, Toronto, ON, Canada (AE).

Abstract

Women who carry a deleterious mutation in BRCA1 or BRCA2 have high lifetime risks of breast and ovarian cancers. However, the influence of a family history of these cancers on these risks in women with BRCA mutations is unclear. We calculated cancer incidence rates for a multinational cohort comprising 3011 women with BRCA1 or BRCA2 mutations who were followed up for a mean of 3.9 years, during which time 243 incident breast or ovarian cancers were recorded. The 10-year cumulative risks of breast cancer were 18.1% (95% confidence interval [CI] = 13.3% to 22.8%) for women with a BRCA1 mutation and 15.2% (95% CI = 9.1% to 21.2%) for women with a BRCA2 mutation. Among women with a BRCA1 mutation, the risk of breast cancer increased by 1.2-fold for each first-degree relative with breast cancer before age 50 years (hazard ratio [HR] = 1.21; 95% confidence interval [CI] = 0.94 to 1.57) and the risk of ovarian cancer increased by 1.6 fold for each first- or second-degree relative with ovarian cancer (HR = 1.61; 95% CI = 1.21 to 2.14). Among women with a BRCA2 mutation, the risk of breast cancer increased by 1.7-fold for each first-degree relative younger than 50 years with breast cancer (HR = 1.67; 95% CI = 1.04 to 2.07).

Clin Genet. 2009 Mar;75(3):220-4.

Breast and ovarian cancer risk perception after prophylactic salpingo-oophorectomy due to an inherited mutation in the BRCA1 or BRCA2 gene.

Finch A, Metcalfe K, Lui J, Springate C, Demsky R, Armel S, Rosen B, Murphy J, Elit L, Sun P, Narod S.

Women’s College Research Institute, Toronto, ON, Canada.

Abstract

It is often recommended that women who carry a mutation in the BRCA1 or BRCA2 gene have their ovaries and fallopian tubes removed to reduce their risk of gynecologic cancer. The aim of this study was to evaluate women’s perception of their risk of breast and ovarian cancer before and after prophylactic salpingo-oophorectomy. We surveyed 127 women who carry a BRCA1 or BRCA2 mutation and who underwent prophylactic salpingo-oophorectomy at the University Health Network, Toronto. Subjects were asked to estimate their risks of breast and ovarian cancer before and after surgery. Their perceived risks of cancers were then compared with published risks, based on their mutation status. BRCA1 carriers estimated their risk of breast cancer risk to be, on average, 69% before surgery and 41% after surgery. They estimated their risk of ovarian cancer to be 55% before surgery and 11% after surgery. BRCA2 carriers estimated their risk of breast cancer to be 69% prior to surgery and 45% after surgery and their perceived risk of ovarian cancer to be 43% before surgery and 8% after surgery. Compared with published risk figures, the perceived risk of ovarian cancer before prophylactic salpingo-oophorectomy was overestimated by 47% of BRCA1 mutation carriers and by 61% of BRCA2 mutation carriers. Most women who have undergone genetic counseling and subsequently choose prophylactic salpingo-oophorectomy accurately perceive their risk of breast cancer. However, in this study, many women overestimated their risk of ovarian cancer, particularly women who carry a BRCA2 mutation.

Expert Analysis Highlights:

• Day before surgery can be an intimidating and confusing time
• Patients who do well the day before surgery describe being active with others
• Contrary to popular opinion, the days before surgery should be an active time with good hearty meals
• Exercising beforehand can set back atrophy by not allowing it to get a head start
• Remember the details of your instructions before surgery

The day before surgery can be an intimidating and confusing time. Anxiety about the outcome of the operation and long-term survival can be alleviated by knowing facts about surgery and tips patients have found useful in preparing.

First, stay active and eat well right up until the night before surgery. Unless you’re having colon surgery which often requires a bowel prep and an extra day of a restricted diet before surgery, go ahead and beef up! Contrary to popular opinion, the days before surgery should be an active time with good hearty meals. I tell many patients to treat themselves to a delicious meal in the days leading up to surgery and, depending on the operation, even the night before surgery. You won’t be eating much after the operation for a couple days at least, so to minimize the period of going without nutrition, its good to get some good calories in the system. Nutrition is also known to strengthen your immune system, which sometimes needs to work well during your recovery.

Along the same lines, stay fit. Go ahead and go to the gym and get some good exercise before surgery. The days after surgery are like being an astronaut in that your muscles get weak from lack of use (called atrophy). Exercising beforehand can set back atrophy by not allowing it to get a head start.

Here are some more facts that are good to ease fears. The data on surgery demonstrate that the operation itself is very standardized. In my field of pancreas surgery for example, nearly every experienced pancreas surgeon in the world performs essentially the same operation with minimal variation. Many patients are also worried about general anesthesia, perhaps based on scary movies or public legends of the olden days, but general anesthesia today has a major complication rate of only about 1 in 100,000. Anesthesia is very safe in the modern era, and its safety profile in medicine is among the best of any medical intervention.

Patients who do well the day before surgery describe being active with others. As a general note on patients that I see who are depressed and anxious, the more someone has a community, the less likely they are to experience depression or anxiety. Movies, performances, getting together with friends, and family gatherings are some of the activities patients find helpful in making the day before surgery a pleasant experience. Often times patients describe a great experience surrounding themselves with positive friends—people who are optimistic and enjoy life.

Finally, remember the details of your instructions before surgery: Nothing to eat or drink by mouth 8 hours before your scheduled surgery time, and bring your most recent CAT scan with you if your surgeon does not already have it.



There are many options for breast reconstructive surgery. One of the more popular is the TRAM flap, especially for a woman with excess belly fat or an abdomen that has been stretched out by pregnancy. You end up with a “tummy tuck”; as a fringe benefit of surgery. I like this video because it shows some nice anatomical drawings that explain the operation.

At many Breast Centers, including our own at Johns Hopkins, the TRAM flap has been replaced by the DIEP flap of abdominal tissue. This has the advantage of not taking any of the rectus abdominal muscle and thus decreases the risk of abdominal weakness or hernias.

Here’s more information from patientresource.net:

Breast reconstructive surgery is done by an experienced plastic surgeon. This surgery is usually done at the time of total mastectomy or later (within months after mastectomy).

Immediate reconstruction can be done for early-stage (stage I or some stage II) breast cnacers, but it is usually best to wait for reconstruction if the breast cancer is more advanced (stage III or some stage II). Increasingly, a “skin-sparing mastectomy” and temporary breast implants are used as the initial process of breast reconstructive surgery, with the final stages of reconstruction performed after all the cancer treatments are completed. If you are to have a mastectomy and think you will want reconstructive surgery, it is best to discuss your choice with your cancer surgeon and a plastic surgeon before the mastectomy so they can properly plan your treatment, even if the reconstructive surgery will not be done until later.

Reconstructive surgery cannot be done for all types of breast cancer. Women who do not want or cannot have reconstructive surgery can be fitted with a breast prosthesis. This prosthesis is a breast form (made of artificial materials) that you put in your bra to make your breast look natural and balanced.

This video segment discusses nipple-sparing mastectomy for breast cancer by surgical oncologists from Case Western Reserve Hospital. This procedure is not applicable for most women facing a total mastectomy and breast reconstruction. However, in carefully selected patients where there is minimal risk for leaving breast cancer behind, it can be an option for women. We have published very good results from our experience at the Avon Foundation Breast Center at Johns Hopkins. A lot of surgical skill goes into doing this procedure correctly.

Here’s more information from patientresource.net:

A mastectomy is necessary for larger tumors or scattered tumors in the breast. Treatment guidelines developed by the National Comprehensive Cancer Network (NCCN) recommend that women with stage IIIA, IIIB, or IIIC breast cancer receive neoadjuvant chemotherapy before mastectomy. Some women with small tumors may wish to have a mastectomy because it offers greater peace of mind about recurrences in the breast or late complications associated with radiation. A mastectomy instead of lumpectomy may also be desired in order to avoid the need for breast radiation therapy altogether.

Because of advances in surgical techniques and knowledge about breast cancer, most mastectomies performed today are much less extensive and disfiguring than those done a decade or two ago. Mastectomy once meant removal of the entire breast with cancer, the chest wall muscles underneath the breast, and all the axillary nodes. This type of mastectomy is called a radical mastectomy, and it is rarely done, and only for extensive tumors or tumors that have invaded the chest wall. Most often, a total mastectomy is performed, which preserves the underlying muscles.

In this blog, I reference three medical articles that provide important information about how breast cancer patients can navigate through a very complex decision-making process and arrive at a treatment plan that is right for them—both to treat their cancer optimally, and also to maximize their quality of life.

The first is a very informative article published in the Journal of Clinical Oncology (JCO) entitled, “Can Women with Early Stage Breast Cancer Make an Informed Decision for Mastectomy?” (Collins ED et al; JCO 27:519-525, 2009). The second is another JCO article titled, “Decision Aids in Breast Cancer: Do They Influence Choice for Surgery and Knowledge of Treatment Options?” ( Waljee JF et al; JCO 25:1067-1073, 2007). Both the 2009 and 2007 articles demonstrate that decision aids for breast cancer patients significantly increase knowledge about breast cancer and treatment options, decrease decision conflict, and increase satisfaction with the decision-making process. Finally, I will quote from a very elegant and thoughtful editorial by Doctors Throckmorton and Esserman ( University of California at San Francisco) titled “When informed, all women do not prefer breast conservation” (JCO 27:484-486, 2009).

In one of the JCO articles, the authors stated: “In general, health literacy is correlated with improved patient outcomes, and patients with inadequate knowledge of their disease states are more likely to be hospitalized and have poorer decision management capabilities. The authors concluded that: “Decision aids have an important role in the treatment process for women with early stage breast cancer… The decision aids increased patient knowledge of treatment options and provided patients with more realistic expectations of outcomes”.

In the other JCO article, the authors assessed the value of a video decision aid and a patient assessment aid. And found that “a notable proportion (35%) of well informed women choose mastectomy. Whereas prior studies have linked objective factors to treatment choice, this study reveals subjective preferences that underlie decision making”.

The authors concluded: “Both researchers and clinicians often view higher rates of breast-conserving treatment as indicative of better care. (Others) caution researchers to ‘move away from a primary focus on rates of mastectomy versus breast–conserving surgery (lumpectomy),and widening the research lens to view the degree to which women are being fully informed.’ This study goes even further to highlight the importance not only of informing patients, but also of eliciting and tailoring care to individual patients’ values and treatment preferences. When women fully comprehend the key facts, many will find that mastectomy, the more invasive procedure, is their preferred choice.”

I will quote from the 2009 JCO editorial that accompanied this article because it beautifully states the approach that all physicians and medical staff should take from the outset of their encounters with a breast cancer patient.

“There are genuine differences between treatment choices among women with similar presentation. It is because the (treatment) options are associated with equivalent survival that it is so critical to make sure that women are full participants in the decision-making process….When informed patients meet with surgeons who are aware of patient values and preferences, the uncertainty resolved for almost all patients…This suggests that if we provide women with the salient facts (in an understandable language), elicit their preferences, and discuss the options in that context, they come to a consultation better informed and more involved in the process.”

‘What the clinician should take away from these studies is that there is great benefit to providing educational materials before consultation; that measuring patient knowledge can help expose gaps in patient understanding of the options; and that there are key questions that the physician can ask to help ensure that the patient is making a decision concordant with her values.”

“The key to offering a choice is respecting the choices patients make. Some people will choose one path, others a different one, we need to accept that women will have different values and will make different choices. Our job is to make sure patients have the choices, the information, the time, and the environment to make an informed, value-driven decision.”

I sure agree with these approaches and their use of educational decision aids! This is an underpinning philosophy on why we spend the time to write blogs and search the internet for informative and trustworthy videos. I repeatedly stated in our Patient Resource Cancer Guides that: “an informed educated patients will almost always get better care” (see our companion website to get a free copy at patientresource.net.

See some of my previous blogs on breast cancer: “Choosing Between a Mastectomy and Lumpectomy” and “Surgical Treatment Options for Breast Cancer”. For those who want a thorough review, see my blog on a 52 minute lecture by Dr Laura Esserman titled “A Detailed Review of Breast Cancer”.

For more written information about breast cancer treatment options, including various types of breast surgery, see our companion website at www.patientresource.net

In many of my blogs about breast cancer treatment options, I have emphasized the importance of patient-based, doctor-guided decision-making. This video, from Beth Israel Medical Center, nicely illustrates the many options of breast reconstruction surgery for breast cancer patients. It tells the story of diverse opinions through a number of patients and why they chose a particular form of reconstructive surgery. Dr Mark Smith is the reconstructive surgeon. Please note that this video shows some graphic operating room scenes.

Here’s more information from our companion website, patientresource.net:

Breast reconstructive surgery is done by an experienced plastic surgeon. This surgery is usually done at the time of total mastectomy or later (within months after mastectomy).

Immediate reconstruction can be done for early-stage (stage I or some stage II) breast cnacers, but it is usually best to wait for reconstruction if the breast cancer is more advanced (stage III or some stage II). Increasingly, a “skin-sparing mastectomy” and temporary breast implants are used as the initial process of breast reconstructive surgery, with the final stages of reconstruction performed after all the cancer treatments are completed. If you are to have a mastectomy and think you will want reconstructive surgery, it is best to discuss your choice with your cancer surgeon and a plastic surgeon before the mastectomy so they can properly plan your treatment, even if the reconstructive surgery will not be done until later.

Reconstructive surgery cannot be done for all types of breast cancer. Women who do not want or cannot have reconstructive surgery can be fitted with a breast prosthesis. This prosthesis is a breast form (made of artificial materials) that you put in your bra to make your breast look natural and balanced.

I recently saw a re-run of an interview on Oprah with Christina Applegate, and she explained why she chose a double mastectomy for the treatment and prevention of breast cancer. I cannot share the Oprah video, but above is another good segment discussing this topic.If you want to see a text version of her interview, go here to Oprah’s website.

Christina Applegate and Sheryl Crow both had breast cancer, but they chose a different surgical treatment for their disease. Christina chose double mastectomy with breast reconstructive surgery while Sheryl Crow chose a lumpectomy only. See my blogs on Sheryl Crow at http://mycanceradvisor.com/2009/04/20/121/ and http://mycanceradvisor.com/2009/06/28/cheryl-crow-talks-with-her-surgeon-about-her-experience-with-breast-cancer/.

As Christina Applegate discussed on the Oprah Winfrey Show, she was very satisfied with her choice and with the results. Likewise, when Sheryl Crow discussed her results on YouTube (with her surgeon no less) she was very satisfied with the symmetry of her breast after surgery. These two stars illustrate how different choices can lead to appropriate results in individual breast cancer patients. Sometimes the size or multiple areas of breast cancer will medically necessitate a mastectomy. In other circumstances a woman may choose a single mastectomy (or a double mastectomy) out of concern for recurrences in the breast at a later time. In effect they are choosing a form of cancer prevention through a mastectomy. On the other hand, a lumpectomy (almost always with breast irradiation) is another equally good option for other women who want to keep their breasts in tact and understand that there is a possibility (of 8-10%) that their breast cancer will return in one or the other breast. Women who have a strong family history, who have had multiple biopsies, who have difficult breasts to follow on X-ray, or who have inherited susceptibility genes (BRAC-1/2), or certain types of breast cancer (especially Lobular Carcinoma) are at increased risk for having a second breast cancer at a later time. If a woman chooses this option, then careful follow-up with screening and chemo prevention (with hormone therapy) should be their treatment plan.

For Christina Applegate, she won’t ever have to have a mammogram again or worry about the prospects of recurring breast cancer or of dying from it. Both choices are medically appropriate and must be tailored to the “risk avoidance” philosophy of the patient and their own perception about how the surgical choice affects their quality of life.

She has formed a Foundation that helps women at high risk for breast cancer that do not have adequate insurance or financial capability to cover essential breast screenings get financial help. See her website at http://www.rightactionforwomen.org/.

For more information about this subject see my previous blogs on Surgical Treatment Options for Breast Cancer and In the Operating Room: Breast Reconstruction. For detailed information about breast cancer staging and treatment go to our companion website, patientresource.net.