A Personalized Approach to Cancer Treatment: How Biomarkers Can Help

Abstract Background: The present approach to cancer treatment is often referred to as “trial and error” or “one size fits all.” This practice is inefficient and frequently results in inappropriate therapy and treatment-related toxicity. In contrast, personalized treatment has the potential to increase efficacy and decrease toxicity. Content: We reviewed the literature relevant to prognostic, predictive, and toxicity-related markers in cancer, with particular attention to systematic reviews, prospective randomized trials, and guidelines issued by expert panels. To achieve personalized treatment for cancer, we need markers for determining prognosis, predicting response to therapy, and predicting severe toxicity related to treatment. Among the best-validated prognostic markers currently available are serum concentrations of α-fetoprotein (AFP), human chorionic gonadotropin (hCG), and lactate dehydrogenase (LDH) for patients with nonseminoma germ cell tumors and tissue concentrations of both urokinase plasminogen activator and plasminogen activator inhibitor 1 (PAI-1) for breast cancer patients. Clinically useful therapy predictive markers are estrogen and progesterone receptors to select patients with breast cancer for treatment with endocrine therapy and human epidermal growth factor receptor 2 (HER-2) to select breast cancer patients for treatment with trastuzumab (Herceptin). Markers available for identifying drug-induced adverse reactions include thiopurine methyltransferase (TPMT) to predict toxicity from thiopurines in the treatment of acute lymphoblastic leukemia and uridine diphosphate glucuronyltransferase to predict toxicity from irinotecan in the treatment of colorectal cancer. Conclusions: Validated prognostic, predictive, and toxicity markers should help cancer treatment move from the current trial-and-error approach to more personalized treatment.

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The effects of an individualized exercise intervention on body composition in breast cancer patients undergoing treatment

Sao Paulo Medical Journal ◽

10.1590/s1516-31802007000100005 ◽

2007 ◽

Vol 125 (1) ◽

pp. 22-28 ◽

Cited By ~ 54

Author(s):

Claudio Battaglini ◽

Martim Bottaro ◽

Carolyn Dennehy ◽

Logan Rae ◽

Edgar Shields ◽

...

Keyword(s):

Breast Cancer ◽

Body Composition ◽

Resistance Training ◽

Cancer Treatment ◽

Cancer Patients ◽

Exercise Intervention ◽

Exercise Group ◽

Moderate Intensity ◽

Control Group ◽

Breast Cancer Patients

CONTEXT AND OBJECTIVE: Changes in metabolism have been reported in the majority of patients undergoing cancer treatment, and these are usually characterized by progressive change in body composition. The effects of aerobic exercise programs to combat the cancer and cancer treatment-related side effects, which include the negative changes in body composition, have been extensively reported in the literature. However, few resistance exercise intervention studies have hypothesized that breast cancer patients might benefit from this type of exercise. The purpose of this study was to determine whether exercise protocols that emphasize resistance training would change body composition and strength in breast cancer patients undergoing treatment. DESIGN AND SETTING: Randomized controlled trial, at the Campus Recreation Center and Rocky Mountain Cancer Rehabilitation Institute of the University of Northern Colorado, and the North Colorado Medical Center. METHODS: Twenty inactive breast cancer patients were randomly assigned to a 21-week exercise group (n = 10) or a control group (n = 10). The exercise group trained at low to moderate intensity for 60 minutes on two days/week. The primary outcome measurements included body composition (skinfold method) and muscle strength (one repetition maximum). RESULTS: Significant differences in lean body mass, body fat and strength (p = 0.004, p = 0.004, p = 0.025, respectively) were observed between the groups at the end of the study. CONCLUSION: The results suggest that exercise emphasizing resistance training promotes positive changes in body composition and strength in breast cancer patients undergoing treatment.

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Probiotics for the Treatment of Docetaxel-Related Weight Gain of Breast Cancer Patients—A Single-Center, Randomized, Double-Blind, and Placebo-Controlled Trial

Frontiers in Nutrition ◽

10.3389/fnut.2021.762929 ◽

2021 ◽

Vol 8 ◽

Author(s):

Zhang Juan ◽

Zhang Qing ◽

Liang Yongping ◽

Liyuan Qian ◽

Wei Wu ◽

...

Keyword(s):

Breast Cancer ◽

Body Weight ◽

Weight Gain ◽

Cancer Treatment ◽

Cancer Patients ◽

Body Fat ◽

Breast Cancer Treatment ◽

Body Fat Percentage ◽

Breast Cancer Patients ◽

Fat Percentage

Background: Docetaxel is an important chemotherapy-agent for breast cancer treatment. One of its side-effects is weight gain, which increases the all-cause mortality rate. Considering gut microbiota is one important factor for weight regulation, we hypothesized that probiotics could be potentially used to reduce the docetaxel-related weight gain in breast cancer patients.Methods: From 10/8/2018 to 10/17/2019, 100 breast cancer (Stage I-III) patients underwent four cycles of docetaxel-based chemotherapy were enrolled and randomly assigned to receive probiotics (Bifidobacterium longum, Lactobacillus acidophilus, and Enterococcus faecalis) or placebo (supplementary material of the probiotics capsule) treatment for 84 days with three capsules per time, twice/day. The primary outcome: the changes in body weight and body-fat percentage of the patients were measured by a designated physician using a fat analyzer, and the secondary outcomes: the fasting insulin, plasma glucose, and lipids were directly obtained from the Hospital Information System (HIS); The metabolites were measured using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS); The fecal microbiome was analyzed using bacterial 16S ribosomal RNA (rRNA) gene sequence. All indicators were measured 1 day before the first cycle of docetaxel-based chemotherapy and 21 days after the last cycle of docetaxel-based chemotherapy.Results: Compared with the placebo group, the probiotic group showed significantly smaller changes in body weight (Mean [SD] 0.77 [2.58] vs. 2.70 [3.08], P = 0.03), body-fat percentage (Mean [SD] 0.04 [1.14] vs. 3.86 [11.09], P = 0.02), and low density lipoprotein (LDL) (Mean [SD]−0.05[0.68] vs. 0.39 [0.58], P = 0.002). Moreover, five of the 340 detected plasma metabolites showed significant differences between the two groups. The change of biliverdin dihydrochloride (B = −0.724, P = 0.02) was inverse correlated with weight gain. One strain of the phylum and three strains of the genus were detected to be significantly different between the two groups. Also, the changes of Bacteroides (B = −0.917, P < 0.001) and Anaerostipes (B = −0.894, P < 0.001) were inverse correlated with the change of LDL.Conclusions: Probiotics supplement during docetaxel-based chemotherapy for breast cancer treatment may help to reduce the increase in body weight, body-fat percentage, plasma LDL, and minimize the metabolic changes and gut dysbacteriosis.Clinical Trial Registration:http://www.chictr.org.cn/showproj.aspx?proj=24294, ChiCTR-INQ-17014181.

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COVID-19 outcomes in patients with a history of breast cancer: A diverse multicenter Los Angeles cohort study.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e12544 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e12544-e12544

Author(s):

Nikhita Kathuria-Prakash ◽

Lauren Antrim ◽

Alexander W Sun ◽

Irene Kang ◽

Maria De Lourdes Garcia-Jimenez ◽

...

Keyword(s):

Breast Cancer ◽

Cohort Study ◽

Los Angeles ◽

Cancer Treatment ◽

Cancer Patients ◽

Hospitalization Rate ◽

Breast Cancer Patients ◽

Treatment History ◽

History Of ◽

Extent Of Disease

e12544 Background: Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 has affected over 100 million individuals during the current pandemic. Cancer is a reported risk factor for worse outcomes from SARS-CoV-2 infection and its clinical syndrome COVID-19. However, risk associated with specific cancer subtypes, extent of disease, and treatment history remains unclear. Breast cancer is the most common cancer in women and is treated with multiple modalities that may affect COVID-19 severity and outcomes, including surgery, radiation (RT), hormone therapy (HT), and chemotherapy (CT). Methods: We conducted a retrospective cohort study of patients with SARS-CoV-2 and history of breast cancer at two academic centers in Los Angeles, CA between January – September, 2020. Demographic information, cancer diagnosis, treatment history, comorbid conditions, and clinical outcomes of COVID-19 were reviewed. The primary outcome was rate of hospitalization for COVID-19. Associations were evaluated for significance by chi-square test or Student’s T test, with a = 0.05. Results: Our cohort included 61 patients with history of breast cancer. 19 (31.1%) required hospitalization and 3 (4.9%) died from COVID-19. Median age was 61 years. 44% of patients were White/Caucasian, 37.7% Hispanic/Latinx, 8% Black/African American, 5% Asian, and 5% were of another race. 87% of patients had local or regional disease and 13% had distant metastases. 53% of patients had ever received CT historically, 66% HT, and 53% RT. 25% of patients received cancer treatment (surgery, CT, or RT) within 90 days of COVID-19 diagnosis. 38% were on HT at time of COVID-19 diagnosis. Patients with prior RT were more likely to be hospitalized from COVID-19 than those with no prior RT (44% vs 14%, p = 0.02), as were patients with 2 or more comorbidities (p = 0.01). In addition, there was a trend toward lower hospitalization rates for patients on HT [24% vs. 42% (p = 0.17)] and a trend toward higher hospitalization rate for non-white ethnicity [35% vs. 25% (p = ns)]. Extent of disease, history of CT, or receipt of any cancer treatment (e.g. surgery, RT, CT) within 90 days of COVID-19 diagnosis were not associated with hospitalization rate. Conclusions: In our diverse cohort of breast cancer patients with COVID-19 a history of RT and presence of multiple comorbidities were both associated with increased risk of hospitalization, while a history of HT was not. Further investigation is needed to validate these findings in larger cohorts. These findings may inform recommendations for breast cancer patients during the ongoing SARS-CoV-2 pandemic.

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Tumor-Biological Factors Upa and PAI-1 as Stratification Criteria of a Multicenter Adjuvant Chemotherapy Trial in Node-Negative Breast Cancer

The International Journal of Biological Markers ◽

10.1177/172460080001500114 ◽

2000 ◽

Vol 15 (1) ◽

pp. 73-78 ◽

Cited By ~ 16

Author(s):

A. Prechtl ◽

N. Harbeck ◽

C. Thomssen ◽

C. Meisner ◽

M. Braun ◽

...

Keyword(s):

Breast Cancer ◽

Adjuvant Chemotherapy ◽

Cancer Patients ◽

Plasminogen Activator ◽

Systemic Therapy ◽

Axillary Node ◽

Breast Cancer Patients ◽

Node Negative ◽

Node Negative Breast Cancer ◽

Pai 1

In axillary node-negative primary breast cancer, 70% of the patients will be cured by locoregional treatment alone. Therefore, adjuvant systemic therapy is only needed for those 30% of node-negative patients who will relapse after primary therapy and eventually die of metastases. Traditional histomorphological and clinical factors do not provide sufficient information to allow accurate risk group assessment in order to identify node-negative patients who might benefit from adjuvant systemic therapy. In the last decade various groups have reported a strong and statistically independent prognostic impact of the serine protease uPA (urokinase-type plasminogen activator) and its inhibitor PAI-1 (plasminogen activator inhibitor type 1) in node-negative breast cancer patients. Based on these data, a prospective multicenter therapy trial in node-negative breast cancer patients was started in Germany in June 1993, supported by the German Research Association (DFG). Axillary node-negative breast cancer patients with high levels of either or both proteolytic factors in the tumor tissue were randomized to adjuvant CMF chemotherapy versus observation only. Recruitment was continued until the end of 1998, by which time 684 patients had been enrolled. Since then, patients have been followed up in order to assess the value of uPA and PAI-1 determination as an adequate selection criterion for adjuvant chemotherapy in node-negative breast cancer patients. This paper reports on the rationale and design of this prospective multicenter clinical trial, which may have an impact on future policies in prognosis-oriented treatment strategies.

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Circulating Ca 15.3 Levels in Breast Cancer. Our Present Experience

The International Journal of Biological Markers ◽

10.1177/172460088600100206 ◽

1986 ◽

Vol 1 (2) ◽

pp. 89-92 ◽

Cited By ~ 18

Author(s):

Ramon Colomer ◽

Alvaro Ruibal ◽

Matilde Navarro ◽

Gloria Encabo ◽

Luis Alfonso Sole ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Objective Response ◽

Stage Iv ◽

Distant Metastases ◽

Response To Therapy ◽

Breast Cancer Patients ◽

Benign Diseases ◽

Ca 15.3 ◽

Stage Iv Breast Cancer

CA 15.3 is an antigen expressed by human breast carcinoma cells, and defined by two monoclonal antibodies, 115D8 and DF3. We used IRMA to determine the circulating serum levels of CA 15.3 in 1178 subjects with breast cancer, non-breast malignancies, benign diseases and controls. A threshold level of 40 U/ml was established with 140 healthy controls and 650 patients with benign diseases (respectively 0% subjects and 1.5% patients had abnormal antigen levels). Elevated CA 15.3 was found in 12 of 184 patients with malignancies different from breast cancer (6.5%), either epithelial carcinomas with distant metastases, mainly in the liver, or primary liver tumors. Breast cancer patients (n=204) were analysed by prior therapy, UICC stage and WHO response to therapy. Eight of 134 (5.9%) patients with stage II or III breast cancer at presentation and no evidence of disease (NED) had elevated CA 15.3. All of 22 patients with stage IV breast cancer not responding to therapy (SD and PD) had antigen levels > 40 U/ml, as did 10 of 34 (29.4%) stage IV patients in objective response (CR+PR). Three of 14 pretreatment patients had abnormal marker levels, and they later proved to have distant metastases. Serum CA 15.3 values were statistically different (p < 0.01) in NED (20.6 ± 11.2 U/ml), CR+PR (33.5 ± 24.0 U/ml), stable disease (98.8 ± 50.4 U/ml) and progressive disease (> 200 U/ml) breast cancer patients. Our results suggest that circulating CA 15.3 antigen levels agree with the stage of breast cancer and with the response to therapy.

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Factors influencing options in primary breast cancer treatment.

Journal of Clinical Oncology ◽

10.1200/jco.1987.5.1.68 ◽

1987 ◽

Vol 5 (1) ◽

pp. 68-74 ◽

Cited By ~ 42

Author(s):

W H Wolberg ◽

M A Tanner ◽

E P Romsaas ◽

D L Trump ◽

J F Malec

Keyword(s):

Breast Cancer ◽

Cancer Treatment ◽

Cancer Patients ◽

Primary Breast Cancer ◽

Breast Cancer Treatment ◽

Cancer Information ◽

Breast Cancer Patients ◽

Term Survival ◽

Tumor Excision ◽

Factors Influencing

Primary breast cancer treatment is determined by tumor factors and by patient preference. Breast cancer treatments that preserve the cosmetic appearance of the breast are appealing and effective for appropriately selected patients; long-term survival following tumor excision and breast irradiation appears to be comparable to that for mastectomy. Since April 1981, when a protocol was developed and treatment options were offered, factors influencing treatment selection have been analyzed in 206 consecutive primary breast cancer patients. Mastectomy was dictated by tumor-related factors in 96 patients (47%); 110 patients (53%) had the option of mastectomy or conservation--tumor excision plus radiotherapy to the breast. Among these 110 eligible patients, 54 chose conservation (49%) and 56 chose mastectomy (51%). Intraoperative findings for ten patients electing conservation necessitated mastectomy, so conservation was accomplished for 44 (21%) of those treated for breast cancer. Beginning in July 1982, breast cancer patients took a battery of psychosexual assessments before any operation (Profile of Mood States [POMS], Health Locus of Control Scale [HLCS] Locke-Wallace Marital Adjustment Test [MAT], Psychosocial Adjustment to Illness Scale [PAIS], Derogatis Sexual Function Inventory [DSFI], Millon Clinical Multiaxial Inventory [MCMI], and a Breast Cancer Information Test [BCIT]). Comparisons of psychologic and demographic variables were made between patients who chose mastectomy and those who chose conservation. No demographic variable was statistically significantly related to choice, although older women tended to select mastectomy more than younger women. Compared with those who elected conservation, women who elected mastectomy were more tense and anxious (P less than .01), more introverted (P less than .01), felt more depressed and dejected (P less than .05), and reported more sexual problems (P less than .05). Those who elected conservation valued their physical appearance more highly (P less than .01) and were generally more self-interested (P less than .05). Mastectomy was dictated by medical considerations for approximately half of patients with breast cancer. Among candidates for breast conservation, the importance of retaining the breast appeared to be determined to a significant degree by measurable psychological factors.

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