• No results found

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(n= 203).

RECEPTOR STATUS FREQUENCY PERCENTAGE (%)

ER+VE 94 46.3 ER-VE 111 54.7

PR+VE 59 29.1

PR-VE 146 71.9

HER-2 +VE 50 24.6 HER2 –VE

Triple -VE

155 76

76.4 37.4

46.3% expressed ER+, while 24.6% expressed HER-2+ status.

54.7% expressed ER-, 71.9% expressed PR-, and 76.4% expressed HER-2 negative.

Overall, 76 patients (37.4%) of tumours were triple negative.

Table 5b: Percentage distribution of receptor-status

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(n= 203).

Receptor-type Frequency Percentage (%)

ER-, PR+, HER2- ER-, PR-, HER2+

ER+, PR-, HER2- ER+, PR+, HER2+

ER+, PR+, HER2- ER-, PR-, HER2- Ungrouped cases

10 11 24 27 32 76 23

4.9 5.4 11.8 13.3 15.8 37.4 11.4

203 100.0

Majority (37.4%) were triple receptor negative, while 15.8% and 13.3% were Luminal A (ER+, PR+, HER2-) and Luminal B (ER+, PR+, HER2+)

respectively.

Table 6: Association of ER, PR, HER-2 of breast cancer

patients with age (n=203).

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Age (years) Total

20 - 30 31 - 40 41 - 50 51 - 60 61 - 70 > 70 X2 p

ER+VE 9(39.1%) 19(36.5%) 36(51.4%) 20(55.6%) 6(40.0%) 2(33.3%) 92 5.898 .435

ER-VE 14(60.9%) 33(63.5%) 34(48.6%) 16(44.4%) 9(60.0%) 4(66.7%) 111

PR+VE 5(21.7%) 15(28.8%) 23(32.9%) 11(30.6%) 3(20.0%) 0(0.0%) 57 4.591 .597

PR-VE 18(78.3%) 37(71.2%) 47(67.1%) 25(69.4%) 12(80.0%) 6(100%) 146

HER-2 +VE 6(26.1%) 11(21.2%) 14(20.0%) 12(33.3%) 3(20.0%) 2(33.3%) 48 3.373 .761

HER2 -VE 17(73.9%) 41(78.8%) 56(80.0%) 24(66.7%) 12(80.0%) 4(66.7%) 155

X2 = chi-square P= p-value

Majority of patients were seen in their 4th-5th decade of life (ER 51.4%; PR 67.1%; HER-2 80%).

The p-values in the table above ranged from 0.435 – 0.761 : (p> 0.05) for ER (0.435), PR (0.597) and HER-2 (0.761) receptor-statuses. No demonstrable association found.

There were no association found between age and the receptor-statuses.

Table 7: Association of ER, PR, HER2 with stage of the

disease (n=203).

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Stage 2 Stage 3 Stage 4 total X2 P

ER+VE 2(50%) 83(44.9%) 7(50.0%) 92 .175 .916

ER-VE 2(50.0%) 102(55.1%) 7(50.0%) 111

PR+VE 2(50.0%) 52(28.1%) 3(21.4%) 57 1.258 .533

PR-VE 2(50.0%) 133(71.9%) 11(78.6%) 146

HER-2 +VE 0(0.0%) 46(24.0%) 2(14.3%) 48 2.070 .355

HER2 -VE 4(100%) 139(75.1%) 12(85.7%) 155

X2 = chi-square P= p-value

Majority were in stage 3 disease at presentation.

The p-values in the table above ranged from 0.916 – 0.355 (p>0.05).

Oestrogen receptor (ER) had p-value of 0.916, while PR had p-value of 0.533.

HER-2 had 0.355.

All values of p were > 0.05.

Therefore there was no demonstrable association between the stage of disease and the receptor-statuses of the patients.

Table 8: Association of ER, PR, HER-2 with duration of

symptoms of patients with breast cancer (n=203).

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<4months 5-8months 9-12months 13months

and above. Total X2 P

ER+VE 36 (40.9%) 26 (44.1%) 27 (52.9%) 3(60.0%) 92 2.358 .501

ER-VE 52(59.1%) 33(55.9%) 24(47.1%) 2(40.0%) 111

PR+VE 19(21.6%) 15(25.4%) 21(41.2%) 2(40.0%) 57 6.724 .081

PR-VE 69(78.4%) 44(74.6%) 30(58.8%) 3(60.0%) 146

HER-2 +VE 29(33.0%) 12(20.3%) 7(13.7%) 0(0.0%) 48 8.909 .061

HER2 -VE 59(67.0%) 47(79.7%) 44(86.3%) 5(100%) 155

X2 = chi-square P= p-value

The expressed ER had a p-value of 0.501 (p>0.05) when correlated with duration of symptoms; PR had 0.081 (p>0.05) while HER-2 had 0.061 (p>0.05).

The p-values were all greater than 0.05 (p>0.05).

With p-values greater than 0.05, there were no demonstrable association found between the duration of symptoms and the receptor-statuses.

Table 9: Correlation of the menstrual state of patients with

the receptor status. (n = 203).

55 Postmenopausal

Not applicable

(Male) Premenopausal

X2 P

ER+VE 32(47.8%) 1(50.0%) 59(44.0%) 92 .269 .874

ER-VE 35(52.2%) 1(50.0%) 75(56.0%) 111

PR+VE 18(26.9%) 0(0.0%) 39(29.1%) 57 .899 .638

PR-VE 49(73.1%) 2(100%) 95(70.9%) 146

HER-2 +VE 17(25.4%) 0(0.0%) 31(23.1%) 48 .750 .687

HER2 -VE 50(74.6%) 2(100%) 103(76.9%) 155

X2 = chi-square P= p-value

Table 9 above revealed all analysis had a p-value > 0.05.

Majority of patients were premenopausal.

The p-value in ER was 0.874 (p>0.05), PR 0.638 (p>0.05) and HER-2 0.687 (p>0.05).

No association was found between the menstrual status and the receptor-status.

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Table 10: The nodal status of patients with breast cancer and their receptor statuses (n=203).

Nodal Status Total X2 P Nodal

negative Nodal positive

ER+VE 5(45.5%) 87(45.3%) 92 0.000 .993

ER-VE 6(54.5%) 105(54.7%) 111

PR+VE 5(45.5%) 52(27.1%) 57 1.739 .187

PR-VE 6(54.5%) 140(72.9%) 146

HER-2 +VE 2(18.2%) 46(24.0%) 48 0.192 .661

HER2 –VE 9(81.8%) 146(76.0%) 155

X2 = chi-square P= p-value

The p-value for ER was 0.993 (p>0.05), PR 0.187 (p>0.05), while HER-2 had 0.661 (p>0.05). The respective p-values had p-values >0.05.

No association was therefore found between nodal status and receptor-status.

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Table 11: Correlation of receptor status with Tumour sizes in patients with breast cancers. (n=203).

Tumour Size group Total

<5x5cm (small

size)

6x6cm-9x9cm (large

size)

10x10cm-14x14cm(ver

y large size)

>14cm(extre mely large

size)

X2 P

ER+VE 1(100%) 29(50.9) 36(43.9%) 26(41.3) 92 2.400 .494 ER-VE 0(0.0%) 28(49.1) 46(56.1%) 37(58.7) 111

PR+VE 0(0.0%) 18(31.6) 25(30.5%) 14(22.2) 57 2.042 .564

PR-VE 1(100%) 39(68.4) 57(69.5%) 49(77.8) 146

HER-2+

0(0.0%)

9(15.8%) 19(23.2%) 20(31.7) 48 4.558 .207

HER2 - 1(100%) 48(84.2) 63(76.8%) 43(68.3) 155

X2 = chi-square P= p-value

The p-values in table 11 above revealed 0.494 for ER (p>0.05), 0.564 for PR (p>0.05) and 0.207 for HER-2 (p>0.05).

The corresponding p-values were greater than 0.05 (p>0.05).

No demonstrable association was found between tumour sizes and receptor-status.

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Table 12: Percentage distribution of disease complications of patients at presentation (n=230).

Complication(s) Frequency Percentage (%) Fungating breast ulcer 10 4.3

Lung metastasis 4 1.7

Liver metastasis 23 10.0

Limb oedema 8 3.5

Weight loss 1 0.4 Peau’d orange 43 18.8

Bone pains 4 1.7

Jaundice 3 1.4

Anaemia 4 1.7

Wieght loss+metastases+bone pains+ulcer+oedema 130 56.5

Total 230 100.0

Majority of patients (56.5% of patients) of patients had weight loss, metastases (lung or liver), bone pains, breast ulcers, peau d’orange and upper limb oedema at presentation and were with complications. All the patients had one form of

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disease complications or the other at presentation.

Table 13: Percentage distribution of disease (metastatic) complications during study period.

(n=203).

Complication(s) Frequency Percentage (%) Bone pain 14 6.9

Lung metastasis 11 5.4

Liver metastasis 11 5.4

Limb oedema 11 5.4

Weight loss 60 29.6 Fungating ulcer 5 2.3

Death 3 1.5

Total 115 56.5

More than half of 203 patients (56.5%) that enrolled for the study had complications during the study period.

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Table 14:Percentage distribution of Infective(non-metastatic) complications in patients with breast cancers

(n=203).

Complication(s) Frequency Percentage (%)

Congestive cardiac failure 2 1.0

Infections 97 47.8

Septicaemia 2 1.0

Total 101 49.8

Majority (47.8%) of patients studied were noted to have infections probably due to decrease immunity from mitotic lesion and administered chemotherapy. And two patients (1.0%) out of 203-patients had septicaemia (probably from surgical site infection) and congestive cardiac failure (probably from Trastuzumab therapy).

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Table 15: Correlation of morbidity of patients with breast cancer and receptor -status (n=102).

Receptor Frequency Morbidity (%) X2 P

ER+ 38 37.3 5.381 0.020 ER- 64 62.7 PR+ 14 13.7 20.914 0.001 PR- 88 86.3

HER2+ 28 27.5 4.747 0.029 HER2- 74 72.5

X2 = chi-square P= p-value

Most of the patients showed negative receptor statuses (ER- 62.7%; PR- 86.3%;

HER2- 72.5%) in their tumours and were with higher percentage of complications of weight loss, lymph oedema of limbs and lung metastasis.

The p-values ranged from 0.020 – 0.029 (p < 0.05), reflecting their significant associations with receptor status. ER had 0.020 p-value; PR 0.001; HER-2 0.029.

There was demonstrable association between receptor-status and disease morbidity.

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Chapter 6

DISCUSSION

A longitudinal study of 203 patients with histologically confirmed breast cancer who equally gave informed consent was carried out between 1st June, 2009 and 31st May, 2011. Tumour characteristics that were correlated in the study included:

stage, histological type, receptor-status, nodal involvement, tumour size, age at presentation, menopausal state and duration of symptoms.

The study revealed patients with breast cancer that presented to LUTH had a high percentage of triple negative receptors (37.4%) in their tumours. This is in support of a previous report that demonstrated triple negative phenotype is more common in African populations including women with Nigerian ancestry26. The study also concord with other previous studies in West Africa that claimed majority of breast cancer are hormone receptor negative23, 36, 41-47. In addition the study is also supported by some studies whose reports observed that patients with breast cancer in West African nations such as Nigeria and Ghana were characterised by early-onset disease coupled with higher rates of triple negative tumours 24-26.

Much has also been documented about the triple negative breast cancer in Western populations where it accounts for approximately 10 – 15% of all breast cancer cases 10. A study of African populations in United States revealed triple negative rates of 20 - 21% 27. In Chinese populations (Asian) study, triple negative tumours

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accounted for 19% 28. In Korea, triple negatives accounted for 14.7% 28, while in a Japanese study, triple negatives accounted for only 7%29. Previous study in Western countries attributed aggressiveness of breast cancer tumours seen in developing countries to high percentage of negative receptor statuses of the tumours at molecular level in these countries47.

The age distribution in this study revealed a mean age of 45.1years at diagnosis with a standard deviation of ± 12.2 years. This is in conformity with previous findings that African breast cancer incidence peaks between the ages of 35 and 45 years, approximately 10-15 years earlier than the peak incidence for western countries 18, 21, 24, 25, 27, 34, 40, 42, 46, 47, 59.

Majority of patients in this study presented with stage III (91.1%) disease, 6.9%

presented at stage IV, and were aggressive with short duration of disease history;

2.0% at stage II; none presented at stage I. This is in agreement with the studies that revealed breast cancer in African women are characterised by relatively advanced stage at presentation. Various studies have reported that 70-90% of African women presented with stage III or IV disease30, 42, 66. A previous study in Lagos, in Nigeria also collaborated the above by reporting that most patients with breast carcinoma presented at late stages; 77% at stage III and stage IV, while only 23% presented at stages I and II19.

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The greater percentage of tumours in this study had short duration of symptoms with most patients presenting within 4 – 12 months of noticing a lump in their breast. This is in agreement with an earlier study which found that majority of patients in Nigeria had brief symptom duration of 3months or less102. This demonstrated the aggressiveness of these tumours. This conforms to study that confirmed breast cancer in West Africa is associated with aggressive features 31.

Despite their short duration of symptoms at presentation, study revealed that majority of patients presented with large tumour sizes at presentation. Their tumour sizes clustered around 5cm x 5cm to 10cm x 10cm. Therefore, this study is not in agreement with previous studies in South Africa that demonstrated that delays among black Africans resulted in significantly larger tumours28, 40. Patients in this study presented barely few months of noticing symptoms yet, they had larger tumour sizes.

In this study, majority of patients were in premenopausal state. One hundred and thirty four patients (67.0%) were premenopausal, while 66 patients (33.0%) were menopausal. This is in agreement with previous studies which documented that African breast cancer patients are more likely to be premenopausal30, 102.

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This study is also in agreement with a study by Chiedozi 85 which confirmed that breast cancer in Nigeria was noted to be a disease of the premenopausal and peri-menopausal females85.

Majority of patients with breast cancer that presented to LUTH during the study period were node positive. This is in conformity with previous studies that demonstrated African-American women in United State have tumours that are not only oestrogen receptor-negative, but also high-grade tumours that are node-positive30, 66, 90, 91, 102. It is also in agreement with a study in South Africa that revealed tumours in Africa are more advanced with nodal pathology compared with white South Africans40.

Majority (185 patients, 91.1%) of patients with breast cancer that presented at LUTH during the period of study had invasive ductal carcinoma as the predominant histologic type. This is in agreement with previous studies which showed majority of breast cancers (approximately 85%) among African women are invasive ductal type30, 73.During the study period 3 deaths were recorded. These resulted possibly from consequences of the disease which may be mainly from distant metastasis to the lungs, bones and other organs. Overall 56.5% of patients had demonstrable distant metastasis at the conclusion of the 2-year study. A greater number of patients with distant metastasis were oestrogen, progesterone and human epidermal growth factor receptor-2 negative. Disease complications showed demonstrable significant association with receptor-statuses of the tumour (p< 0.05). The treatment administered to these patients at LUTH included: surgery

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(135.3 patients; 66.67%, mastectomy), chemotherapy (203 patients; 100%, adjuvant chemotherapy), radiotherapy (50.7patients; 29.97%) and hormonal therapy (67.7 patients; 33.35%, Tamoxifen).

Chapter 7

CONCLUSION

In this study, result analysis revealed that Nigerian women with breast cancers that presented to LUTH during the study period did not completely conform to previous studies which revealed that African women with breast cancers demonstrated substantial number of triple negative tumours, late presentation, young age at diagnosis, premenopausal mainly, low response to hormonal therapy with poor treatment outcome.

This study did not completely conform to previous studies because majority of patients in the study presented early as at the time of presentation. They also had a good rather than low response to hormonal therapy as almost half of patients do not progress to disease complications following hormonal therapy. However majority had a high receptor-negativity (37.4%) and were seen in rapid tumour progression demonstrated by short duration of symptoms.

In conclusion, patients with breast cancer seen at LUTH during the study period demonstrated a high predominance of triple receptor negativity with aggressive behaviour depicted in short duration of symptoms. Majority presented early and were not only

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premenopausal but also of young age group. The disease stages at presentation were advanced and were of larger sizes with regional lymph nodes involvement. None among tumour characteristics except disease complications demonstrated significant correlation with receptor-status. No patient in the study showed low response to hormonal therapy.

Chapter 8

RECOMMENDATIONS

Based on the findings from this study the followings recommendations are made.

1. The provision of modern facilities in our teaching hospitals capable of estimating receptor-status will help improve the management of patients with breast cancers as it is obtained in most developed health centres of the world today.

2. Immuno-histochemical analysis of breast cancer cells should be mandatory as minimum requirement in the management of breast cancer.

3. Need for establishment or creation of Dedicated Breast Clinics to provide services relating mainly to breast lesions. Also Special training of health professionals as relates to breast cancer and its burden should be embarked on to tackle the challenges in the successful management of breast cancers in our country, Nigeria.

4. Awareness campaigns should be amplified to encourage early presentations of our people with breast cancers.

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