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What Is Oligometastatic Breast Cancer

Papers Of Particular Interest Published Recently Have Been Highlighted As: Of Importance Of Major Importance

Oligometastatic breast cancer treatment
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    Jain SK, Dorn PL, Chmura SJ, Weichselbaum RR, Hasan Y. Incidence and implications of oligometastatic breast cancer. J Clin Oncol. 2012 30:e11512.

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    Hellman S, Weichselbaum RR. Oligometastases. J Clin Oncol. 1995 13:810. This is the original paper that defined oligometastasis.

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    Halsted WS. I. the results of operations for the cure of cancer of the breast performed at the Johns Hopkins Hospital from June, 1889, to January, 1894. Ann Surg. 1894 20:497555.

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    Halsted WS. The results of radical operations for the cure of carcinoma of the breast.*. Ann Surg. 1907 46:119.

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    Hortobagyi GN, Connolly JL, DOrsi CJ, Edge SB, Mittendorf EA, Rugo HS, Solin LJ, Weaver DL, Winchester DJ, Giuliano A Breast. In: AJCC Cancer Staging Man. Springer International Publishing, Cham, pp 589636.

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  • Associations With Overall Survival And Progression

    The 10-year OS estimate for patients with no more than 3 metastases was 14.9% vs 3.4% for patients with more than 3 metastases , based on the weighted cohort. Factors independently associated with better OS in patients with OMBC included premenopausal and perimenopausal status, absence of lung metastases, and local therapy of metastases and the primary tumor . Single-organ metastases was not independently associated with better OS. In comparison, local therapy of metastases was not associated with better OS in all patients with MBC .

    In patients with OMBC, the same factors were associated with better PFS as with OS: premenopausal and perimenopausal status, absence of lung metastases, local therapy of metastases, and local therapy of the primary tumor .

    Role Of Adjuvant Or Pseudoadjuvant Systemic Therapy

    Borner et al. reported the first randomized trial in OMBC wherein patients with good-risk isolated locoregional recurrence were randomized, after local treatment, to receive tamoxifen or not. Tamoxifen improved the median disease free survival from 26 to 82 months but OS was not significantly increased, perhaps because of small sample size and short follow-up.

    Chemotherapy in the so called pseudoadjuvant setting has been supported mainly by phase II trials. The largest data is from M. D. Anderson Cancer Center which published the outcome of patients in four phase II trials utilizing combined modality for the treatment of isolated recurrences. Patients received local therapy with curative intent and efficacy of adjuvant chemotherapy in subjects with clinical CR was evaluated. Three of the 4 studies used doxorubicin based chemotherapy and after a median follow-up of 121.5 months the estimated 20-year DFS and OS were both 26% in these studies. With a shorter median followup in the docetaxel based trial, the DFS was 58%. However, potential selection bias and inclusion of anthracycline and taxane naïve patients in these studies makes their results less generalizable.

    Role of neoadjuvant like chemotherapy

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    Locoregional Treatment Of The Primary

    Retrospective series of thousands of patients consistently show an overall survival advantage 0.65-0.70) from radical’ management of the primary tumor, either by surgery or definitive RT , in patients presenting with MBC. Possible explanations include: i) patient selection bias ii) restoration of immunocompetence by removal of immunosuppressive factors iii) decreased tumor burden in the body iv) removal of the seed’ source of new metastases v) decrease in potentially resistant cell lines and vi) increased chemosensitivity due to angiogenesis in distant disease sites instigated by surgery. It is not clear which patients most likely benefit from treatment of the primary tumor: those with estrogen-responsive tumors, bone metastases only, low disease burden at diagnosis, or those who respond to ST?

    Some potential disadvantages of surgery have arisen with the primary tumor being a source of antiangiogenic factors and growth factor inhibitors, an accelerated relapse might follow its removal . The possible release of growth factors related to surgical wounding and the immunosuppression caused by surgery and anesthesia are also potential drawbacks. At the same time, improvements in surgery and anesthesia have led to a significant reduction in morbidity, resulting in more patients being able to benefit from this approach.

    Rt For Oligometastatic Bone Disease In Bca

    Example of (oligometastatic) M+/ disease detected by 68 ...

    Few studies suggest RT for treatment of patients with oligometastatic bone disease in BCa . In these studies, only a single patient presented grade 3 acute dermatitis with grade â¥3 toxicity. Overall, patients received a high radiation dose that resulted in favorable outcomes, and mild toxicities. Here, Milano et al. reported that the 5- and 10-year OS rates after SBRT were 83% and 75%, respectively, for bone-only patients vs. 31% and 17%, respectively, for other patients . Next, Rades et al. suggest that the outcomes were most favorable in patients with myeloma/lymphoma followed by those with BCa, and that none of the BCa patients showed progression of motor deficits. Additionally, Yoo et al. reported that high-dose RT and HER2-negative status were significantly associated with improved local control, and Takemoto et al. reported that local recurrence was observed in a patient treated with 3 Gy Ã10 irradiation, the lowest dose among the eleven patients.

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    Few Mets Could Mean Curative Treatment

    Weichselbaums acceptance speech, Oligometastasis from Conception to Treatment, will be published in the Journal of Clinical Oncology in the fall. In the interim, you can read Hanan Goldbergs excellent summary here.

    Oligometastasis describes patients who have only a few metastatic spots that are typically confined to one organ. Being oligometastatic means maybe, just maybe, you have a chance of being curedprovided you are treated aggressively and your cancer responds.

    Reportedly there are more than 90,000 oligometastatic disease presentations in the four most common cancers in the US every year. This includes 10,000 prostate cancer patients, 14,000 breast cancer patients, 14,000 colorectal cancer patients and 50,000 lung cancer patients.

    In 1999, Dr. Weichselbaum and his University of Chicago colleague, Samuel Hellman made the controversial suggestion that many patients with oligometastatic disease could be cured, depending on the extent of disease burden, with either surgery or targeted radiation therapy. As U of Cs John Easton reports, this notion, the spectrum theory of metastasis, has slowly been accepted, backed by a mounting series of reports of successful treatments.

    Therapeutic Options For Oligometastases

    Radiation therapy

    While much of the literature supporting the oligometastatic states is within the surgical literature, there is an increasing body of literature describing the use of stereotactic body radiotherapy and stereotactic radiosurgery , in addition to conventional fractionated radiotherapy techniques . SBRT is a noninvasive method of delivering high doses of radiation to ablate a target lesion while sparing the neighboring normal tissue, thus reducing long-term effects of radiation on the non-malignant tissues. The radiation is delivered from many beams originating from multiple directions that converge on the target site. Through improved targeting and management of tumor motion, SBRT may improve tumor control and reduce treatment-related toxicity, as compared to conventional fractionated RT. Improved radiation targeting allows for higher-dose, hypofractionated, more efficient treatment regimens that can be delivered within narrow margins sparring adjacent organs. Hypofractionation is the delivery of large doses of radiation over a shorter time period as compared to conventional radiation fraction sizes. Therapy can generally be completed in 15 sessions, as compared to conventional radiation therapy that is delivered in smaller doses 5 days/week over 6 weeks.

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    Do Advances In Systemic Therapy Change Mdt

    In addition to more aggressive use of surgery and radiation directed at specific metastases, recent improvements in systemic therapies are altering the disease course of breast cancer and have potential implications on how and when to incorporate MDT. For example, the recent CLEOPATRA study changed standard of care for patients with metastatic HER2 positive breast cancer after demonstrating improved OS and PFS for patients receiving pertuzumab, trastuzumab, and docetaxel compared to placebo, trastuzumab, and docetaxel . In hormone receptor positive, HER2 negative metastatic breast cancer, cyclin-dependent kinase 4/6 inhibitors including palbociclib, ribociclib, and abemaciclib, are now being used in addition to hormonal therapy after multiple randomized phase III trials demonstrated their use improves PFS and/or OS . Other targeted agents such as PI3K and PARP inhibitors are also being incorporated into the treatment of metastatic breast cancer to improve outcomes .

    Testing The Concept In Clinical Trials

    Oligometastatic breast cancer

    The gold standard for research that typically moves the needle of cancer care is a clinical trial, particularly a large trial that randomly assigns participants to one of two groups, each of which receive different treatments.

    Only a handful of randomized clinical trials have specifically enrolled patients with oligometastatic cancer and tested direct treatment of their metastatic tumors, and most of these have been relatively small.

    One such trial, called SABR-COMET, enrolled approximately 100 patients with any type of solid cancer as long as they had five or fewer metastases. Participants were randomly assigned to the standard treatment for their particular cancer or the standard treatment and a targeted form of radiation called stereotactic body radiation therapy also known as SABRto treat their metastases.

    When initial results were published 2 years ago, trial researchers reported that patients in the SBRT group lived more than a year longer than those in the control group.

    The trial has received some criticism, however. Among the critiques is that there were many more patients with prostate cancer in the SBRT group than the control group. Prostate cancer patients with metastases live longer than patients with other metastatic cancers , Dr. Vikram said, and this imbalance could likely have accounted for the better outcomes in that group.

    There are many questions about the concept of oligometastatic cancer that still need to be answered, Dr. Salama added.

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    Oligometastatic Breast Cancer: Sabr Extends Long

    Key clinical point: Stereotactic ablative body radiotherapy leads to long-term systemic disease control and survival in patients with oligometastatic breast cancer.

    Major finding: The median follow-up was 50 months. Of the patients who progressed, 82% had new metastases and 18% experienced local failure. Median overall survival was 86 months, and progression-free survival was 33 months. The receipt of SABR within 5 years of diagnosis and presence of triple-negative breast cancer were associated with worse OS. Advanced T stage and TNBC were associated with worse PFS.

    Study details: A retrospective study of patients with metastatic breast cancer who received SABR between 2008 and 2018.

    Disclosures: This study was supported by the National Institutes of Health/National Cancer Institute. The authors declared no conflicts of interest.

    Wijetunga NA et al. Cancer Med. 2021 Jun 22. doi: 10.1002/cam4.4068 .

    Rt For Oligometastatic Bone Disease In Other Primary Sites

    Some studies have opted RT for oligometastatic bone disease in other primary sites , and 8 of these 10 studies have used stereotactic body radiation therapy . Sixty-seven percent of Grade â¥3 toxicities were fractures requiring a surgery. Overall, they resulted in excellent outcomes with mild toxicities.

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    Metastatic Breast Cancer Symptoms And Diagnosis

    The symptoms of metastatic breast cancer can vary greatly depending on the location of the cancer. This section covers the symptoms of breast cancer that has spread to the bone, lung, brain, and liver, and the tests used to diagnose metastatic breast cancer.

    Bone Metastasis: Symptoms and DiagnosisThe most common symptom of breast cancer that has spread to the bone is a sudden, noticeable new pain. Breast cancer can spread to any bone, but most often spreads to the ribs, spine, pelvis, or the long bones in the arms and legs. Learn more.

    Lung Metastasis: Symptoms and DiagnosisWhen breast cancer moves into the lung, it often doesnt cause symptoms. If a lung metastasis does cause symptoms, they may include pain or discomfort in the lung, shortness of breath, persistent cough, and others. Learn more.

    Brain Metastasis: Symptoms and DiagnosisSymptoms of breast cancer that has spread to the brain can include headache, changes in speech or vision, memory problems, and others. Learn more.

    Liver Metastasis: Symptoms and DiagnosisWhen breast cancer spreads to the liver, it often doesnt cause symptoms. If a liver metastasis does cause symptoms, they can include pain or discomfort in the mid-section, fatigue and weakness, weight loss or poor appetite, fever, and others. Learn more.

    A More Treatable Kind Of Metastatic Cancer

    Cureus

    A plan for stereotactic body radiation therapy to treat a metastatic lung tumor.

    Rarely are the terms cure and metastatic cancer used together. Thats because cancer that has spread from where it originated in the body to other organs is responsible for most deaths from the disease.

    But in 1995, two cancer researchers put forth a controversial concept: There is a state of cancer metastasis that isnt necessarily fatal. They called it oligometastatic cancer, describing it as existing between a cancer that is contained to where it originated and one that has spread extensively throughout the body.

    In oligometastatic cancer, the patient has only a few, usually small metastases . For some patients, this form of metastatic cancer should be amenable to a curative therapeutic strategy, Ralph Weichselbaum, M.D., and Samuel Hellman, M.D., both from the University of Chicago, wrote some 25 years ago.

    At the time, and still today, most people with metastatic cancer are treated only with therapies meant to kill cancer cells anywhere they may be in the body, known as systemic treatment. The assumption being that any evidence of metastatic cancer, Dr. Weichselbaum said, means that metastases are everywhere, and thats not necessarily true.

    Its taken time, but over the last 5 years or so, the duos hypothesis has been put to the test, primarily in small clinical trials.

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    Are Oligometastases Common In Breast Cancer

    While evidence supporting the oligometastatic state was sparse when Hellman and Weichselbaum first proposed their theory, since then numerous studies have demonstrated oligometastases to be fairly common. Among patients with metastatic breast cancer enrolled on major phase II and phase III clinical trials of systemic therapies, approximately 50% present with two or fewer clinically detected metastases . Similar rates of oligometastases are seen in patients with NSCLC, melanoma, prostate cancer, and colorectal cancer .

    Additionally, patients with oligometastatic breast cancer have been shown to have better outcomes than patients with widespread metastases. Data from the 1980s demonstrated that among patients with metastatic breast cancer, the presence of five or fewer metastases was an independent predictor of survival . More recent data has shown that patients with early-stage breast cancer who progressed with five or fewer metastases have improved five-year and median survival compared to patients with more than five metastases . Similarly, studies have shown improved outcomes for patients with oligometastatic prostate cancer and NSCLC compared to patients with widespread disease . Taken together, it is clear that oligometastatic disease, including breast cancer, is relatively common and has meaningful clinical significance.

    Metastatic Breast Cancer Treatment And Planning

    After a diagnosis of metastatic breast cancer, its helpful to take all the time you need to gather information and make decisions about your treatment. Learn about the medical specialists that may be involved in your care, treatment options, genetic testing, taking a break from treatment, and more.

    SurgeryDoctors sometimes recommend surgery for metastatic breast cancer in order, for example, to prevent broken bones or cancer cell blockages in the liver. Learn more.

    ChemotherapyChemotherapy is used in the treatment of metastatic breast cancer to damage or destroy the cancer cells as much as possible. Learn more.

    Radiation TherapyYour doctor may suggest radiation therapy if youre having symptoms for reasons such as easing pain and controlling the cancer in a specific area. Learn more.

    Hormonal TherapyHormonal therapy medicines are used to help shrink or slow the growth of hormone-receptor-positive metastatic breast cancer. Learn more.

    Targeted TherapyTargeted therapies target specific characteristics of cancer cells, such as a protein that allows the cancer cells to grow in a rapid or abnormal way. Learn more.

    Local Treatments for Distant Areas of MetastasisLocal treatments are directed specifically to the new locations of the breast cancer such as the bones or liver. These treatments may be recommended if, for example, the metastatic breast cancer is causing pain. Learn more.

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    Oligometastatic Lung Cancer: How Should It Be Managed

    Cancer has historically been divided between localized and metastatic disease. The underlying principle, derived from the Halsted theory of cancer progression, is that once cancer has spread to other sites, it is a systemic disease. Heroic efforts to remove or ablate all evidence of visible cancer thus would expose patients to toxicity without a chance for benefit.

    Joshua M. Bauml, MD

    Cancer has historically been divided between localized and metastatic disease. The underlying principle, derived from the Halsted theory of cancer progression, is that once cancer has spread to other sites, it is a systemic disease. Heroic efforts to remove or ablate all evidence of visible cancer thus would expose patients to toxicity without a chance for benefit.

    We now know that cancer is not quite so simple. In colorectal cancer, for instance, patients with metastases only to the liver can be cured up to 20% of the time with hepatic resection. Although there is potentially some unique biology surrounding the lymphatic drainage of colorectal cancer, multiple series have shown that oligometastatic disease occurs in a wide range of tumor types. It is important to clarify some terms, however, because many of these retrospective series conflate different clinical situations. These terms do not have widely accepted definitions, but for the purposes of this article, I think we need a shared vocabulary.

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