<?xml version="1.0" encoding="UTF-8"?><!DOCTYPE article  PUBLIC "-//NLM//DTD Journal Publishing DTD v3.0 20080202//EN" "http://dtd.nlm.nih.gov/publishing/3.0/journalpublishing3.dtd"><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" dtd-version="3.0" xml:lang="en" article-type="research article"><front><journal-meta><journal-id journal-id-type="publisher-id">JCT</journal-id><journal-title-group><journal-title>Journal of Cancer Therapy</journal-title></journal-title-group><issn pub-type="epub">2151-1934</issn><publisher><publisher-name>Scientific Research Publishing</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.4236/jct.2022.138046</article-id><article-id pub-id-type="publisher-id">JCT-119366</article-id><article-categories><subj-group subj-group-type="heading"><subject>Articles</subject></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Medicine&amp;Healthcare</subject></subj-group></article-categories><title-group><article-title>
 
 
  Locally Advanced Breast Cancer in Pakistani Women: What Is Different from Rest of the World and Why It Is Difficult to Manage
 
</article-title></title-group><contrib-group><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Muhammad</surname><given-names>Khalid</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Noor</surname><given-names>Ul Wara Rao</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Farwa</surname><given-names>Batool Shamsi</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Tayaba</surname><given-names>Kanwal</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Sana</surname><given-names>Arshad</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Muhammad</surname><given-names>Shahzeb</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Ameer</surname><given-names>Alam</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Sobia</surname><given-names>Aleem</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>M.</surname><given-names>Ahsan Iqbal</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref><xref ref-type="corresp" rid="cor1"><sup>*</sup></xref></contrib></contrib-group><aff id="aff3"><addr-line>Department of PB &amp;amp; Genetics, University of Agriculture, Faisalabad, Pakistan</addr-line></aff><aff id="aff2"><addr-line>Department of Pathology, Faisalabad Medical University (FMU), Faisalabad, Pakistan</addr-line></aff><aff id="aff1"><addr-line>Oncology/CCU, Allied Hospital Faisalabad, Faisalabad Medical University, Faisalabad, Pakistan</addr-line></aff><pub-date pub-type="epub"><day>01</day><month>08</month><year>2022</year></pub-date><volume>13</volume><issue>08</issue><fpage>525</fpage><lpage>530</lpage><history><date date-type="received"><day>16,</day>	<month>May</month>	<year>2022</year></date><date date-type="rev-recd"><day>21,</day>	<month>August</month>	<year>2022</year>	</date><date date-type="accepted"><day>24,</day>	<month>August</month>	<year>2022</year></date></history><permissions><copyright-statement>&#169; Copyright  2014 by authors and Scientific Research Publishing Inc. </copyright-statement><copyright-year>2014</copyright-year><license><license-p>This work is licensed under the Creative Commons Attribution International License (CC BY). http://creativecommons.org/licenses/by/4.0/</license-p></license></permissions><abstract><p>
 
 
  Locally Advance Breast Cancer refers to a heterogeneous group of breast
   cancer with locally extensive disease, which may or may not involve the nodes, without any distant metastases. The study was conducted at Faisalabad Medical University (FMU), Oncology, Allied Hospital Faisalabad (Pakistan). Data of 100 patients with LABC was collected. Demographics were recorded in the form of age, socio-economic status. In clinical data, time of presentation, family history of breast cancer, the presenting symptom in the form of lump, ulceration and other skin changes were noted. Histo-pathological variables including tumor size, histopathology, Bloom &amp; Richardson grading, estrogen receptor (ER), progesterone receptor status (PR) and HER2 status. Results showed that after following a standard trimodality treatment approach in LABC patients, 30 percent died within two years. Disease free survival for more than two years was observed in only 25% of patients. Whereas, 70% patients had eventful (Recurrence/metastases) survival. This poor outcome was observed due to lack of health care facilities, awareness and poor socioeconomic status.
 
</p></abstract><kwd-group><kwd>Oncology Breast</kwd><kwd> Cancer in Pakistani Women</kwd><kwd> LABC</kwd></kwd-group></article-meta></front><body><sec id="s1"><title>1. Introduction</title><p>Cancer is a leading cause of death globally and is responsible for an estimated 9.6 million deaths in the world. Breast cancer is most common among women. Locally advanced breast cancer (LABC) is characterized by the presence of a large primary tumor (&gt;5 cm) or involvement of internal mammary nodes (N1b) associated with or without skin or chest-wall involvement (T4) or with fixed (matted) axillary lymph nodes in the absence of any evidence of distant metastases. LABC may be the result of neglected tumors or if tumor is rapidly growing. These cancers are classified as stage II, lllA and lllB according to the AJCC staging system [<xref ref-type="bibr" rid="scirp.119366-ref1">1</xref>]. Asian countries have higher incidence of LABC compared to the western developed countries due to poor socio-economic status. In India and Pakistan, incidence of LABC is 30% - 60%, Malaysia 50% - 60% and Singapore 21%, while in USA only 10% - 20% of all breast cancers present as LABC [<xref ref-type="bibr" rid="scirp.119366-ref2">2</xref>] [<xref ref-type="bibr" rid="scirp.119366-ref3">3</xref>] [<xref ref-type="bibr" rid="scirp.119366-ref4">4</xref>] [<xref ref-type="bibr" rid="scirp.119366-ref5">5</xref>]. Current recommendation for treating LABC are neo-adjuvant chemotherapy followed by surgery and radiation therapy; hormonal treatment is added for receptor positive disease and Transtuzuumab Therapy for Her2neu positive patients [<xref ref-type="bibr" rid="scirp.119366-ref6">6</xref>] [<xref ref-type="bibr" rid="scirp.119366-ref7">7</xref>] [<xref ref-type="bibr" rid="scirp.119366-ref8">8</xref>] [<xref ref-type="bibr" rid="scirp.119366-ref9">9</xref>]. Despite of multimodality approach outcome is still very poor. Compared to patients with early breast cancer, patients with LABC are at a significantly higher risk of local recurrence and distant metastases. Even in USA, the five year survival rate for women with LABC is 55% [<xref ref-type="bibr" rid="scirp.119366-ref2">2</xref>]. The present study focused at all such factors and their comparison with rest of world so that treatment strategies can be developed for Pakistani women.</p></sec><sec id="s2"><title>2. Materials and Methods</title><p>The study was conducted at Allied Hospital Faisalabad. One hundred patients of locally advance breast cancer were treated during the year 2013 to 2015. The data was collected retro-spectively from medical record of patients which was present in the record room of hospitals Oncology Centre. Out of 100 patients, most of the patients had T3 or N2 disease. Demographics were recorded in the form of age and socio-economic status of the patients. In clinical data, time of presentation, family history of breast cancer, the presenting symptom in the form of lump, ulceration and other skin changes were noted. Histo-pathological variables studied including tumor size, Bloom and Richardson grading, estrogen receptor (ER) and progesterone receptor status (PR) and HER2neu status. All treatment variables were recorded. Patients were put on three-month follow-up for 2 years. The treatment pattern is described in <xref ref-type="table" rid="table1">Table 1</xref>. This table describe the</p><table-wrap id="table1" ><label><xref ref-type="table" rid="table1">Table 1</xref></label><caption><title> Treatment patterns</title></caption><table><tbody><thead><tr><th align="center" valign="middle" >Treatment modality</th><th align="center" valign="middle" >Frequency</th></tr></thead><tr><td align="center" valign="middle" >Neo-Adjuvant Chemotherapy</td><td align="center" valign="middle" >98%</td></tr><tr><td align="center" valign="middle" >MRM with ALND</td><td align="center" valign="middle" >90%</td></tr><tr><td align="center" valign="middle" >Toilet Mastectomy</td><td align="center" valign="middle" >7%</td></tr><tr><td align="center" valign="middle" >Adjuvant Radiotherapy</td><td align="center" valign="middle" >95% 5% develop metastatic disease during the course of neu-adjuvant chemo-therapy or after surgery</td></tr><tr><td align="center" valign="middle" >Hormonal treatment</td><td align="center" valign="middle" >60%</td></tr></tbody></table></table-wrap><p>standard treatment approach for LABC. Neo-Adjuvant Chemo-therapy was done in 98% patients followed by MRM with ALND in 90% patients and Toilet Mastectomy in 7% patients. Ninety five percent (95%) of patients underwent Adjuvant-Radiation Therapy while 5% developed metastatic disease during the treatment.</p></sec><sec id="s3"><title>3. Results</title><p>Patient’s characteristics and presenting symptoms are summarized in <xref ref-type="table" rid="table2">Table 2</xref>(a) and <xref ref-type="table" rid="table2">Table 2</xref>(b). Median age was 45 years. Mostly patients were in the age group of 30 to 60 years. Family history of breast cancer was noted in four patient. Information regarding family history was missing in medical record of five patients. Median duration between noticing lump and seeking medical help was eight months.</p><p>Tumor characteristics are mentioned in <xref ref-type="table" rid="table3">Table 3</xref>. All tumors were either grade ll or grade lll, 60% of patients were ER and PR receptors positive. They all receive hormone therapy. Twenty five percent patients (25%) were HER2neu positive. Only about 40 percent were affording for transtuzumab therapy. Five percent patients (5%) did not get their receptor status done.</p><p>Clinical outcome is mentioned in <xref ref-type="table" rid="table4">Table 4</xref>.</p></sec><sec id="s4"><title>4. Discussion</title><p>We have observed poor outcome of LABC in Pakistani women as compared with developed countries. Although trimodality therapy has improved the outcome but still 30% of LABC patients died at the end of two years after completing their</p><table-wrap-group id="2"><label><xref ref-type="table" rid="table2">Table 2</xref></label><caption><title> (a) Clinical characteristics of patients with LABC (N = 28); (b) Presenting symptoms of patients</title></caption><table-wrap id="2_1"><caption><title> (b)</title></caption><table><tbody><thead><tr><th align="center" valign="middle" >Patients characteristics</th><th align="center" valign="middle" >Frequency</th></tr></thead><tr><td align="center" valign="middle" >Female</td><td align="center" valign="middle" >100%</td></tr><tr><td align="center" valign="middle" >Family H/O breast cancer</td><td align="center" valign="middle" >4%</td></tr><tr><td align="center" valign="middle" >Right sided lesion</td><td align="center" valign="middle" >64%</td></tr><tr><td align="center" valign="middle" >Left sided lesion</td><td align="center" valign="middle" >36%</td></tr><tr><td align="center" valign="middle" >Median Age</td><td align="center" valign="middle" >45 Years</td></tr><tr><td align="center" valign="middle" >Median Duration of presentation</td><td align="center" valign="middle" >8 months</td></tr></tbody></table></table-wrap><table-wrap id="2_2"><caption><title></title></caption><table><tbody><thead><tr><th align="center" valign="middle" >Symptom</th><th align="center" valign="middle" >Frequency</th></tr></thead><tr><td align="center" valign="middle" >Lump with skin ulceration</td><td align="center" valign="middle" >20%</td></tr><tr><td align="center" valign="middle" >Fungating</td><td align="center" valign="middle" >10%</td></tr><tr><td align="center" valign="middle" >Fixed lump</td><td align="center" valign="middle" >70%</td></tr></tbody></table></table-wrap></table-wrap-group><table-wrap id="table3" ><label><xref ref-type="table" rid="table3">Table 3</xref></label><caption><title> Tumor biology</title></caption><table><tbody><thead><tr><th align="center" valign="middle" >Tumor characteristics</th><th align="center" valign="middle" >Frequency</th></tr></thead><tr><td align="center" valign="middle" >IDC</td><td align="center" valign="middle" >96% (4% other histology)</td></tr><tr><td align="center" valign="middle" >Grade ll</td><td align="center" valign="middle" >61%</td></tr><tr><td align="center" valign="middle" >Grade llI</td><td align="center" valign="middle" >39%</td></tr><tr><td align="center" valign="middle" >ER+/PR+</td><td align="center" valign="middle" >60%</td></tr><tr><td align="center" valign="middle" >ER−/PR−</td><td align="center" valign="middle" >40%</td></tr><tr><td align="center" valign="middle" >H2N Positive</td><td align="center" valign="middle" >25%</td></tr><tr><td align="center" valign="middle" >Unknown Receptor status</td><td align="center" valign="middle" >3%</td></tr><tr><td align="center" valign="middle" >Node positive</td><td align="center" valign="middle" >74%</td></tr></tbody></table></table-wrap><table-wrap id="table4" ><label><xref ref-type="table" rid="table4">Table 4</xref></label><caption><title> Clinical outcome of patients</title></caption><table><tbody><thead><tr><th align="center" valign="middle" >Survival</th><th align="center" valign="middle" >Frequency</th></tr></thead><tr><td align="center" valign="middle" >Mortality within 2-years</td><td align="center" valign="middle" >30%</td></tr><tr><td align="center" valign="middle" >Alive more than 2-years</td><td align="center" valign="middle" >70%</td></tr><tr><td align="center" valign="middle" >Disease free survival for more than two years</td><td align="center" valign="middle" >25%</td></tr><tr><td align="center" valign="middle" >Re-currence/metastases in those survived for more than 2-years</td><td align="center" valign="middle" >70%</td></tr></tbody></table></table-wrap><p>treatment. This number can be even more because some patients lost to follow up. Another study on Pakistani women also reported poor outcome [<xref ref-type="bibr" rid="scirp.119366-ref10">10</xref>]. It’s very important to figure out causes of LABC and difficulties being faced by doctors to treat such cases consequently such information will help health authorities to develop plans to deal with LABC in public sector and oncologist to develop management strategies.</p><p>In literature, many studies have identified lack of awareness, fear, lower socioeconomic status and illiteracy as main factors leading to late presentation and ending up in Locally advanced disease [<xref ref-type="bibr" rid="scirp.119366-ref11">11</xref>] [<xref ref-type="bibr" rid="scirp.119366-ref12">12</xref>] [<xref ref-type="bibr" rid="scirp.119366-ref13">13</xref>] [<xref ref-type="bibr" rid="scirp.119366-ref14">14</xref>]. These factors are common among all developing countries including Paskistan [<xref ref-type="bibr" rid="scirp.119366-ref15">15</xref>]. Another important factor which could be the cause of locally advanced disease is its aggressive biological behavior as node positive disease was found in 74 percent patients after surgery. Secondly despite the fact that 60 percent were ER/PR receptor positive and they also received hormone therapy even then they develop recurrence or metastatic disease. Racial differences in biology of carcinoma breast have been well described. Japanese women tend to have less aggressive breast cancer among Asians [<xref ref-type="bibr" rid="scirp.119366-ref6">6</xref>]. Within USA Afro-Americans and Hispanic women have more aggressive disease as compare to others USA [<xref ref-type="bibr" rid="scirp.119366-ref7">7</xref>] [<xref ref-type="bibr" rid="scirp.119366-ref8">8</xref>]. Other factors which are compromising outcome are delay in seeking the treatment and unavailability of adequate oncological services [<xref ref-type="bibr" rid="scirp.119366-ref9">9</xref>] [<xref ref-type="bibr" rid="scirp.119366-ref16">16</xref>]. Surgical services are present in every tertiary care center in Pakistan but very few tertiary centers have parallel oncological services which further compromise the management of LABC patients in our population. When we refer them to oncology centers after surgery, most patients get lost because of economic constraints and long waiting time at such centers. These factors are totally manageable so by increasing awareness and oncological facilities to improve the outcome.</p></sec><sec id="s5"><title>Conflicts of Interest</title><p>There is no conflict of interest. This is a research/analysis based work.</p></sec><sec id="s6"><title>Cite this paper</title><p>Khalid, M., Ul Wara Rao, N., Shamsi, F.B., Kanwal, T., Arshad, S., Shahzeb, M., Alam, A., Aleem, S. and Iqbal, M.A. (2022) Locally Advanced Breast Cancer in Pakistani Women: What Is Different from Rest of the World and Why It Is Difficult to Manage. Journal of Cancer Therapy, 13, 525-530. https://doi.org/10.4236/jct.2022.138046</p></sec></body><back><ref-list><title>References</title><ref id="scirp.119366-ref1"><label>1</label><mixed-citation publication-type="other" xlink:type="simple">Singletary, S.E., Allred, C., Ashley, P., Bassett, L.W., Berry, D., Bland, K.L., et al. (2002) Revision of American Joint Committee on Cancer Staging System for Breast Cancer. Journal of Clinical Oncology, 20, 3628-3636.  
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